An Innovative Formulation Based on Nanostructured Lipid Carriers for Imatinib Delivery: Pre-Formulation, Cellular Uptake and Cytotoxicity Studies

Imatinib (IMT) is a tyrosine kinase enzyme inhibitor and extensively used for the treatment of gastrointestinal stromal tumors (GISTs). A nanostructured lipid carrier system (NLCS) containing IMT was developed by using emulsification–sonication methods. The characterization of the developed formulation was performed in terms of its particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, loading capacity, sterility, syringeability, stability, in vitro release kinetics with mathematical models, cellular uptake studies with flow cytometry, fluorescence microscopy and cytotoxicity for CRL-1739 cells. The particle size, PDI, loading capacity and zeta potential of selected NLCS (F16-IMT) were found to be 96.63 ± 1.87 nm, 0.27 ± 0.15, 96.49 ± 1.46% and −32.7 ± 2.48 mV, respectively. F16-IMT was found to be stable, thermodynamic, sterile and syringeable through an 18 gauze needle. The formulation revealed a Korsmeyer–Peppas drug release model of 53% at 8 h, above 90% of cell viability, 23.61 µM of IC50 and induction of apoptosis in CRL-1739 cell lines. In the future, F16-IMT can be employed to treat GISTs. A small amount of IMT loaded into the NLCSs will be better than IMT alone for therapy for GISTs. Consequently, F16-IMT could prove to be useful for effective GIST treatment.

Characterization and biodistribution of trans resveratrol-PEG-folic acid-gold nanoparticle conjugates

Purpose: To evaluate the characteristics and biodistribution of trans resveratrol-PEG-folic acid-gold nanoparticle conjugates (rsv-PEG-FA-AuNP). Methods: Gold nanoparticles were produced by citric reduction followed by conjugation of PEG-folic acid and resveratrol. Characterization of rsv-PEG-FA-AuNP conjugates including their particle size, zeta potential, and by Fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM) was carried out. Biodistribution study of rsv-PEG-FA-AuNP was carried out using female Sprague Dawley rats. Biodistribution data were obtained from high performance liquid chromatography (HPLC) analysis. Results: The mean particle size and zeta potential of rsv-PEG-FA-AuNP were 249.03 ± 10.31 and - 36.33 ± 3.12 mV, respectively. TEM images showed rsv-PEG-FA-AuNP conjugates formed spherical shape. Rsv-PEG-FA-AuNP conjugates found in plasma, kidney (1.90 ± 0.20 μg/g), spleen (2.65 ± 1.18 μg/g), liver (1.74 ± 0.03 μg/g), and lung (1.82 ± 0.12 μg/g), after 90 minutes intravenous administration (i.v.) in female Sprague Dawley rats. No free resveratrol was found in plasma, kidney, or spleen after i.v administration in female dawdle Sprague Dawley rats. Conclusion: Resveratrol-PEG-FA-AuNP conjugates appear to be a potential chemotherapy delivery system for active targeting purposes because of its longer systemic circulation and its accumulation in the kidney.

Stability and Free Radical Production for CO2 and H2 in Air Nanobubbles in Ethanol Aqueous Solution

In this study, 8% hydrogen (H2) in argon (Ar) and carbon dioxide (CO2) gas nanobubbles was produced at 10, 30, and 50 vol.% of ethanol aqueous solution by the high-speed agitation method with gas. They became stable for a long period (for instance, 20 days), having a high negative zeta potential (−40 to −50 mV) at alkaline near pH 9, especially for 10 vol.% of ethanol aqueous solution. The extended Derjaguin, Landau, Verwey, and Overbeek (DLVO) theory was used to evaluate the nanobubble stability. When the nanobubble in ethanol alkaline aqueous solution changed to an acidic pH of around 5, the zeta potential of nanobubbles was almost zero and the decrease in the number of nanobubbles was identified by the particle trajectory method (Nano site). The collapsed nanobubbles at zero charge were detected thanks to the presence of few free radicals using G-CYPMPO spin trap reagent in electron spin resonance (ESR) spectroscopy. The free radicals produced were superoxide anions at collapsed 8%H2 in Ar nanobubbles and hydroxyl radicals at collapsed CO2 nanobubbles. On the other hand, the collapse of mixed CO2 and H2 in Ar nanobubble showed no free radicals. The possible presence of long-term stable nanobubbles and the absence of free radicals for mixed H2 and CO2 nanobubble would be useful to understand the beverage quality.

Enhanced Anti-Proliferative Effect of Carboplatin in Ovarian Cancer Cells Exploiting Chitosan – Poly (lactic glycolic acid) Nanoparticles.

Objective: The aim of the present article was to enhance the therapeutic efficacy of carboplatin (CP) using the formulation of chitosan – poly (lactic glycolic acid) nanoparticles (CS-PLGA NPs). Methods: Nanoparticles were synthesized by an ionic gelation method and were characterized for their morphology, particle size, and surface potential measurements by TEM and zeta sizer. This study was highlighted for the evaluation of drug entrapment, loading and in vitro drug release capabilities of the prepared nanoparticles by spectrophotometric analysis. The stability study was also conducted after 3 months for their particle size, zeta potential, drug loading and encapsulation efficiencies. Further, ovarian cancer cell line PEO1 were used to evaluate the toxicity and efficacy of nano-formulation by MTT assay. Further, the study was evaluated for apoptosis using flow cytometric analysis. Result: The CS-PLGA-CP NPs were uniform and spherical in shape. The particle size and zeta potential of CS-PLGA-CP NPs were measured 156 ± 6.8 nm and +52 ± 2.4 mV, respectively. High encapsulation (87.4 ± 4.5 %) and controlled retention capacities confirmed the efficiency of the prepared nanoparticles in a time and dose dependant manner. The cytotoxicity assay results also showed that CS-PLGA-CP NPs has high efficiency on PEO1 cells compared to the free drug. The flow cytometric result showed 64.25 % of the PEO1 cells were apoptotic and 8.42 % were necrotic when treated with CS-PLGA-CP NPs. Conclusion: Chitosan-PLGA combinational polymeric nanoparticles were not only steady but also non-toxic. Our experiments revealed that the chitosan- PLGA nanoparticles could be used as a challenging vehicle candidate for drug delivery for the therapeutic treatment of ovarian cancer.

Cyclodextrins-in-Liposomes: A Promising Delivery System for Lippia sidoides and Syzygium aromaticum Essential Oils

Biological activity of essential oils (EOs) has been extensively reported; however, their low aqueous solubility, high photosensitivity, and volatility compromise a broad industrial use of these compounds. To overcome these limitations, we proposed a nanoencapsulation approach to protect EOs, that aims to increase their stability and modulate their release profile. In this study, drug-in-cyclodextrin-in-liposomes encapsulating two essential oils (Lippia sidoides and Syzygium aromaticum) and their respective major compounds (thymol and eugenol) were produced by ethanol injection and freeze-dried to form proliposomes and further physicochemically characterized. Liposomes showed high physical stability over one month of storage at 4 °C, with slight changes in the mean size, polydispersity index (PDI), and zeta potential. Reconstituted proliposomes showed a mean size between 350 and 3300 nm, PDI from 0.29 to 0.41, and zeta potential between −22 and −26 mV. Differential scanning calorimetry and X-ray diffraction of proliposomes revealed a less-ordered crystalline structure, leading to high retention of the major bioactive compounds (between 73% and 93% for eugenol, and 74% and 84% for thymol). This work highlights the advantages of using drug-in-cyclodextrin-in-liposomes as delivery systems to retain volatile compounds, increasing their physicochemical stability and their promising potential to be utilized as carriers in products in the pharmaceutical, food, and cosmetic industries.

PHYSICOCHEMICAL PROPERTIES AND NUTRITION OF MORINGA OLEIFERA LAM. LEAF EXTRACT: A PRELIMINARY STUDY ON PREPARATION PHYTOSOMES AS HERBAL SUPPLEMENT FOR CHILDREN

Objective: The study aimed to evaluate the physicochemical properties and nutrition of Moringa leaf extract. In addition, the preliminary study for the preparation of Moringa leaf extract-loaded phytosomes for a supplement. Methods: Extraction of Moringa leaf made using microwave-assisted extraction, followed by evaluation of proximate analysis (water, total ash, acid-insoluble of ash contents, and residual n-hexane), phytochemical screening, and nutrition such as crude protein, amino acids, and minerals (iron, zinc, and calcium). The phytosomes were prepared by the anti-solvent precipitation method and assessed for the morphology, particle size, zeta potential, polydispersity index (PDI), entrapment efficiency (EE), and Fourier-transform infrared spectra. Results: The nutrition contents of crude protein, iron, zinc, and calcium were 19.61±0.07%, 3.47±0.00 mg/100g, 5.46±0.05 mg/100g, and 747.40±4.89 mg/100g, respectively. The amino acids with the highest concentrations were glutamic acid, phenylalanine, aspartic acid, alanine, and arginine in the extract. The best preparation using sonication 10 min by morphology was a spherical included particle size, PDI, zeta potential, and EE of arginine was 87.16±1.73 nm, 0.22±0.04, −23.07±0.76 mV, and 108.94±0.52%, respectively. Conclusion: These preliminary results provide evidence of the nutritional benefit of Moringa leaf extract-loaded phytosomes as a promising supplement to prevent stunting in children.

pH-Responsive Liposomes of Dioleoyl Phosphatidylethanolamine and Cholesteryl Hemisuccinate for the Enhanced Anticancer Efficacy of Cisplatin

The current study aimed to develop pH-responsive cisplatin-loaded liposomes (CDDP@PLs) via the thin film hydration method. Formulations with varied ratios of dioleoyl phosphatidylethanolamine (DOPE) to cholesteryl hemisuccinate (CHEMS) were investigated to obtain the optimal particle size, zeta potential, entrapment efficiency, in vitro release profile, and stability. The particle size of the CDDP@PLs was in the range of 153.2 ± 3.08–206.4 ± 2.26 nm, zeta potential was −17.8 ± 1.26 to −24.6 ± 1.72, and PDI displayed an acceptable size distribution. Transmission electron microscopy revealed a spherical shape with ~200 nm size. Fourier transform infrared spectroscopic analysis showed the physicochemical stability of CDDP@PLs, and differential scanning calorimetry analysis showed the loss of the crystalline nature of cisplatin in liposomes. In vitro release study of CDDP@PLs at pH 7.4 depicted the lower release rate of cisplatin (less than 40%), and at a pH of 6.5, an almost 65% release rate was achieved compared to the release rate at pH 5.5 (more than 80%) showing the tumor-specific drug release. The cytotoxicity study showed the improved cytotoxicity of CDDP@PLs compared to cisplatin solution in MDA-MB-231 and SK-OV-3 cell lines, and fluorescence microscopy also showed enhanced cellular internalization. The acute toxicity study showed the safety and biocompatibility of the developed carrier system for the potential delivery of chemotherapeutic agents. These studies suggest that CDDP@PLs could be utilized as an efficient delivery system for the enhancement of therapeutic efficacy and to minimize the side effects of chemotherapy by releasing cisplatin at the tumor site.