RESUMEN
This study aimed to develop paclitaxel (PTX)-loaded PEGylated (PEG)-pH-sensitive (SpH) liposomes to enhance drug delivery efficiency and cytotoxicity against MCF-7 breast cancer cells. PTX-loaded PEG-SpH liposomes were prepared using the thin film hydration method. ATR-FTIR compatibility studies revealed no significant interactions among liposome formulation components. TEM images confirmed spherical morphology, stability, and an ideal size range (180-200 nm) for improved blood circulation. At pH 5.5, liposomes exhibited increased size and positive zeta potential, indicating pH-sensitive properties due to CHEMS response to the acidic tumor microenvironment. Conversely, at pH 7.4, liposomes showed a slightly larger size (199.25 ± 1.64 nm) and a more negative zeta potential (-36.94 ± 0.32 mV), suggesting successful PEG-SpH surface modification, enhancing stability, and reducing aggregation. PTX-loaded PEG-SpH liposomes demonstrated high encapsulation efficiency (84.57 ± 0.92% w/w) and drug loading capacity (4.12 ± 0.26% w/w). In-vitro drug release studies revealed accelerated first-order PTX release at pH 5.5 and a controlled zero-order release at pH 7.4. Cellular uptake studies on MCF-7 cells demonstrated enhanced PTX uptake, attributed to mPEG-PCL incorporation prolonging circulation time and CHEMS facilitating PTX release in the tumor microenvironment. Furthermore, PTX-loaded PEG-SpH liposomes exhibited significantly improved cytotoxicity with an IC50 value of 1.107 µM after 72-h incubation, approximately 90% lower than plain PTX solution. Stability studies confirmed the robustness of the liposomal formulation under various storage conditions. These findings highlight the potential of PEGylated pH-responsive liposomes as effective nanocarriers for enhancing PTX therapy against breast cancer.
Asunto(s)
Neoplasias de la Mama , Liberación de Fármacos , Liposomas , Paclitaxel , Polietilenglicoles , Paclitaxel/administración & dosificación , Paclitaxel/farmacología , Paclitaxel/farmacocinética , Paclitaxel/química , Humanos , Liposomas/química , Células MCF-7 , Concentración de Iones de Hidrógeno , Polietilenglicoles/química , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Femenino , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/farmacocinética , Antineoplásicos Fitogénicos/química , Tamaño de la Partícula , Supervivencia Celular/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodosRESUMEN
Aim: This study aimed to formulate erlotinib hydrochloride (ERT-HCL)-loaded chitosan (CS) and poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) using Quality-by-Design (QbD) to optimize critical quality attributes (CQAs). Materials & methods: Quality target product profile (QTPP) and CQAs were initially established. Based on L8-Taguchi screening and risk assessments, central composite design (CCD) design was used to optimize NPs. Results: ERT-HCL-loaded CS-PLGA NPs had a mean particle diameter, zeta potential and entrapment efficiency of 226.50 ± 1.62 d.nm, 27.66 ± 0.64 mV and 78.93 ± 1.94 %w/w, respectively. The NPs exhibited homogenous spherical morphology and sustained release for 72 h. Conclusion: Using systematic QbD approach, ERT-HCL was encapsulated in CS-PLGA NPs, optimizing CQAs. These findings propel future research for improved NSCLC treatment.
Innovative erlotinib-loaded chitosan-PLGA nanoparticles, developed through a systematic QbD approach, promise enhanced drug delivery for NSCLC. Optimized for size, potential and entrapment efficiency, these particles demonstrate sustained release over 72 h. #DrugDelivery #QBD #NSCLC.
Asunto(s)
Quitosano , Clorhidrato de Erlotinib , Ácido Láctico , Nanopartículas , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Clorhidrato de Erlotinib/administración & dosificación , Clorhidrato de Erlotinib/química , Quitosano/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Nanopartículas/química , Ácido Láctico/química , Ácido Poliglicólico/química , Portadores de Fármacos/química , Liberación de Fármacos , Química Farmacéutica/métodos , Preparaciones de Acción Retardada , Antineoplásicos/administración & dosificación , Antineoplásicos/químicaRESUMEN
The study developed and evaluated Sorafenib Tosylate (SRT)-loaded polymeric microparticles (MPs) using biodegradable polymer polycaprolactone (PCL) as a potential inhalable carrier for NSCLC. MPs were prepared by spray-drying an oil-in-water (o/w) emulsion. The optimized MPs demonstrated excellent flowability, particle size of 2.84 ± 0.5 µm, zeta potential of -14.0 ± 1.5 mV, and 85.08 ± 5.43% entrapment efficiency. ATR-FTIR/DSC studies revealed a lack of characteristic peaks of the crystalline drug signifying good entrapment of the drug. MPs were spherical and uniform in SEM pictures. The MPs showed a biphasic release pattern up to 72h. The Anderson cascade impactor (ACI) investigation demonstrated the highest drug deposition at stage 4, which revealed that the MPs can reach the lungs' secondary and terminal bronchi. Inhalable MPs had an efficient aerodynamic property with a mass median aerodynamic diameter (MMAD) of 2.63 ± 1.3 µm, a geometric standard deviation (GSD) of 1.93 ± 0.2 µm, and a fine particle fraction (FPF) of 87 ± 2.5%. Finally, in cytotoxicity studies on A549 cancer cells, MPs had an IC50 value of 0.6011 ± 0.8 µM, which was 85.68% lower than free drug. These findings suggest SRT-loaded inhalable PCL-based MPs as a novel NSCLC treatment.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Células A549 , Sorafenib/farmacología , Poliésteres , Polímeros , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológicoRESUMEN
Non-small cell lung cancer (NSCLC) has a long history of defying traditional cytotoxic treatment. Significant advancements in biotechnology, cancer biology, and immunotherapy have provided new insights that have altered the landscape for the management of NSCLC, clearing the way for a new era of pharmaceuticals in the form of monoclonal antibodies and their fragments. Antibody fragments are superior to monoclonal antibodies because of their small size, which allows them to penetrate cells and tissues effectively. When combined with functional nanocarriers, antibody fragments can target cancer cells while offering improved efficacy and fewer off-target effects. We discuss current topics of interest including anti-CTLA-4 mAbs, Talactoferrin alfa (TLF), and the CYFRA 21-1 biomarker, with brief insights into its novel detection system.