Nebulizable colloidal nanoparticles co-encapsulating a COX-2 inhibitor and a herbal compound for treatment of lung cancer

A challenging disease such as lung cancer requires the combination of different modalities to achieve beneficial therapeutic outcomes. In this work, PLGA nanoparticles were chosen as colloidal carrier for two drugs with reported anti-lung cancer activity: naringin and celecoxib. PLGA nanoparticles were prepared and characterized for their particle size, zeta potential, entrapment efficiency, in vitro release, stability, morphology, cytotoxicity, as well as aerosolization and nebulization behaviors. Their biodistribution pattern upon pulmonary aerosolization, and safety on healthy lung tissues were determined as well. Results showed that the described system displayed a particle size <260 nm with unimodal distribution, entrapment efficiency for celecoxib and naringin reaching 96% and 62% respectively and a controlled release profile for the two drugs. The selected formula displayed favorable nebulization properties with high drug deposition percentages in lower impinger and impactor stages. It also exhibited higher cytotoxic activity on A549 lung cancer cell lines compared to the free drugs combination, while displaying considerable safety on healthy lung tissues. Biodistribution studies delineated the lung deposition potential of the nanoparticles accompanied with high distribution to the bones, brain and liver which are common metastatic sites of lung cancer, proving their promising nature in the treatment of lung cancer

Ethanol-Based Proliposome Delivery Systems of Paclitaxel for In Vitro Application Against Brain Cancer Cells

In this study the anticancer activity of paclitaxel-loaded nano-liposomes on glioma cell lines was investigated. Soya phosphatidylcholine:cholesterol (SPC:Chol), hydrogenated soya phosphatidylcholine:cholesterol (HSPC:Chol) or dipalmitoylphosphatidylcholine:cholesterol (DPPC:Chol) in 1:1 mole ratio were used to prepare ethanol-based proliposomes. Following hydration of proliposomes, the size of resulting vesicles was subsequently reduced to nanometer scale via probe-sonication. The resulting formulations were characterized in terms of size, zeta potential and morphology of the vesicles, and entrapment efficiency of paclitaxel (PX) as well as the final pH of the preparations. DPPC-liposomes entrapped 35–92% of PX compared to 27–74% and 25–60% entrapped by liposomes made from SPC and HSPC formulations respectively, depending on drug concentration. The entrapment efficiency of liposomes was dependent on the lipid bilayer properties and ability of PX to modify surface charge of the vesicles. In vitro cytotoxicity studies revealed that PX-liposome formulations were more selective at inhibiting the malignant cells. The cytotoxicity of PX-liposomes was dependent on their drug-entrapment efficiency. This study has shown PX-liposomes generated from proliposomes have selective activity against glioma cell lines, and the synthetic DPPC phospholipid was most suitable for maximized drug entrapment and highest activity against the malignant cells in vitro

Proliposome Powders for the Generation of Liposomes: the Influence of Carbohydrate Carrier and Separation Conditions on Crystallinity and Entrapment of a Model Antiasthma Steroid

Formulation effects on the entrapment of beclometasone dipropionate (BDP) in liposomes generated by hydration of proliposomes were studied, using the high-density dispersion medium deuterium oxide in comparison to deionized water (DW). Proliposomes incorporating BDP (2 mol% of the lipid phase consisting of soya phosphatidylcholine (SPC) and cholesterol; 1:1) were manufactured, using lactose monohydrate (LMH), sorbitol or D-mannitol as carbohydrate carriers (1:5 w/w lipid to carrier). Following hydration of proliposomes, separation of BDP-entrapped liposomes from the unentrapped (free) BDP at an optimized centrifugation duration of 90 min and a centrifugation force of 15,500g were identified. The dispersion medium was found to have a major influence on separation of BDP-entrapped liposomes from the unentrapped drug. Entrapment efficiency values were higher than 95% as estimated when DW was used. By contrast, the entrapment efficiency was 19.69 ± 5.88, 28.78 ± 4.69 and 34.84 ± 3.62% upon using D2O as a dispersion medium (for LMH-, sorbitol- and D-mannitol-based proliposomes, respectively). The similarity in size of liposomes and BDP crystals was found to be responsible for co-sedimentation of liposomes and free BDP crystals upon centrifugation in DW, giving rise to the falsely high entrapment values estimated. This was remedied by the use of D2O as confirmed by light microscopy, nuclear magnetic resonance ((1)HNMR), X-ray diffraction (XRD) and entrapment studies. This study showed that carrier type has a significant influence on the entrapment of BDP in liposomes generated from proliposomes, and using D2O is essential for accurate determination of steroid entrapment in the vesicles