Preparation irinotecan hydrochloride loaded PEGylated liposomes using novel method supercritical fluid and condition optimized by Box-Behnken design.

A semi-synthetic camptothecin derivative known as irinotecan hydrochloride is frequently used to treat colorectal cancer, including colorectal adenocarcinoma and lung cancers involving small cells. Irinotecan has a very short half-life; therefore, continuous infusions are required to keep the drug's blood levels at therapeutic levels, which could produce cumulative toxicities. Effective delivery techniques, including liposomes, have been developed to address these shortcomings. In this study, a continuous supercritical fluid approach dubbed Expansion Supercritical Fluid into an aqueous solution, in which the pressure decreases rapidly but remains over the critical pressure, is proposed to manufacture polyethylene glycolylated (PEGylated) liposomes carrying irinotecan hydrochloride. To accomplish this, PEGylated liposomes were created using a Box-Behnken design, and the operating parameters (flow rate, temperature, and pressure drop) were optimized. Encapsulation efficiency, mean size, and prepared liposome count were 94.6%, 55 nm, and 758 under ideal circumstances. Additionally, the stability of the PEGylated liposome was investigated during 8 weeks, and also PEGylated liposome-loaded irinotecan release profile was compared to conventional liposomes and free irinotecan, and a constant drug release was seen after the first burst release from liposomes.

Evaluation of curcumin-based ophthalmic nano-emulsion on atropine-induced dry eye in mice.

Background: One of the most efficient treatments for dry eye syndrome (DES) is to use nanocarriers as a potential delivery system. We aim to evaluate curcumin in a nano emulsion formulation. Methods: A new formulation containing 5.5% curcuminoid was used. DLS, Zeta potential, TEM, and HPLC tests were performed to determine the size and morphology. First, 30 mice were selected as atropine-induced dry eye models. Next, 25 mice in 5 groups were treated with the nano emulsion at different doses, and corneal tissues were separated for evaluation. Results: The DLS test results were indicative of the particles' stability. Nano curcumin appeared to be thoroughly effective in all groups, with the highest dose showing the most similarity to the healthy control group. Conclusions: Curcumin-based nano emulsion eye drop is a promising candidate for DES management. However, further investigation is required to evaluate the possible risks in humans.

Production Ganoderma lucidum extract nanoparticles by expansion of supercritical fluid solution and evaluation of the antioxidant ability.

Due to the growing human tendency to treat with natural substances, fungi such as Ganoderma lucidum can be a good source to meet this need. Effectiveness, ease of use and a rich source of active ingredients such as ganoderic acids have caused G. lucidum to be considered in the pharmaceutical and food industries. In this project, G. lucidum was applied to extraction using supercritical carbon dioxide. Then expansion of supercritical fluid solution (ESS) was used as, novel, repeatable and green method to yield nanoparticles from G.lucidum extract. The response surface method was used to improve the Extraction efficiency, antioxidant activity, and improving the nanoparticles production status. Optimal conditions were observed at the extraction step by setting pressure at 27.5 MPa, dynamic time of 46 min, and modifier volume of 162 µL. The optimum point for the production of nanoparticles was obtained as follows: pressure drop at 25 MPa, 20 min for collection time, and 40° C for temperature. Under these conditions, the size and count were 86.13 nm, and 98, respectively. Nanoparticles were analyzed by FESM and, the DPPH was used for antioxidant activity evaluation. The LC-MS identified various ganoderic acids from G.lucidum that are famous to be highly oxygenated triterpenoids.

Micronization of Thebaine Extracted from Papaver bracteatum Lindl. Using Supercritical Fluid Technology.

BACKGROUND: Thebaine, as a main opiate alkaloid extracted from Papaveraceae plants, is widely used in the synthesis of many pharmaceutical ingredients such as buprenorphine, naltrexone, naloxone, and hydrocodone. Nevertheless, thebaine and related derivatives are often insoluble in aqueous media and have low bioavailability in digestive systems. OBJECTIVE: Reducing particle size and changing the morphology can mitigate the mentioned problem. In this study, extraction of thebaine from the capsule, stem, and root of Papaver bracteatum L. was optimized and micronization of extract components was developed to study solubility. METHODS: The extraction process was performed using supercritical carbon dioxide. Experimental central composite design was employed to determine the optimal conditions. Analysis of extract was done using a validated high performance liquid chromatography method and mass spectrometry. The micronization process was performed using an inhouse developed supercritical technique. The nanoparticles were characterized using field emission scanning electron microscopy (FESEM) and ImageJ software. The effect of micronization was explored on the solubility of extract components via ultraviolet spectroscopy. RESULTS: The percentage of thebaine in dried capsule, stem, and root powder was about 1.05, 0.31, and 0.83% respectively. The extraction results indicate that supercritical pressure has the greatest effect on the extraction yield. Analysis of FESEM images revealed that nanoparticles of extract components with particle size distribution of 5-100 nm were collected successfully. CONCLUSION: The extraction results indicate that pressure has the greatest effect on the extraction yield. In vitro studies illustrated that the solubility of extract components increased up to 1.7 times during the micronization process. HIGHLIGHTS: Expansion of supercritical methods as an effective method was performed for extracting and preparing alkaloid nanoparticles. This process led to improved oral bioavailability of alkaloids.

Preparation of Withaferin A nanoparticles extracted from Withania somnifera by the expansion of supercritical fluid solution.

INTRODUCTION: Withania somnifera (L.) Dunal. is a plant with several important medicinal properties that have long been used in traditional therapy to treat some diseases. OBJECTIVE: Micronisation reduces the particle size, which increases the bioavailability. In this study, due to the great potential of Withaferin A in the treatment of diseases, the nanoparticle formation of Withaferin A extracted from Withania somnifera, was considered. METHODOLOGY: In the first step, the experimental parameters of supercritical fluid extraction of W. somnifera were optimised by central composite design (CCD). Then, the herbal extract was micronised using a new, repeatable, and robust method in terms of the expansion of carbon dioxide supercritical solvent. Also, the parameters of the experiment were optimised with the Draper-Lin small composite designs. Moreover, we identified Withaferin A nanoparticle in the extracted samples by utilising liquid chromatography-mass spectrometry (LC-MS) and the obtained precipitates were characterised using field emission scanning electron microscopy (FESEM). RESULTS: The optimal conditions of the experiment were as follows: pressure drop 254 atm, at the temperature of 53°C, equilibrium time 23 min, and collection time 57 min. Based on the observed results, the optimum points for the size and number of Withaferin A nanoparticles were predicted as 5 and 5842 nm, respectively. CONCLUSION: The nanoparticle production was accomplished through the expansion of supercritical solution, while the speed of expansion was much lower compared to the ordinary rapid expansion of supercritical solution (RESS) methods. Also, the nanonisation conditions, especially the pressure drop, significantly affected the formation of nanoparticles.

Downregulation of Matrix Metalloproteinases 2 and 9 is Involved in the Protective Effect of Trehalose on Spinal Cord Injury.

Upregulation of matrix metalloproteinases (MMPs), in particular MMP-2 and MMP-9 contributes to secondary pathogenesis of spinal cord injury (SCI) via promoting inflammation. Recently, we have reported that trehalose suppresses inflammatory responses following SCI. Therefore, we investigated the effect of trehalose on MMP-2 and MMP-9 expression in SCI. A weight-drop contusion SCI was induced in male rats. Then, the animals received trehalose at three doses of 10 (T10), 100 (T100) and 1000 (T1000) mM intrathecally. MMP-2 and MMP-9 transcripts were then measured in damaged spinal cord at 1, 3 and 7 days after trauma, and compared with vehicle and sham groups. Additionally, behavioral analysis was conducted for 1 week using Basso-Beattie-Bresnahan (BBB) locomotor rating scale. Our data showed an early upregulation of MMP-9 at 1 day post-SCI. However, MMP-2 expression was increased at 3 days after trauma. Treatment with 10 mM trehalose significantly reduced MMP-2 expression in 3 and 7 days (P< 0.01) and MMP-9 expression in 1, 3, and 7 days (P< 0.05) post-damage compared with vehicle. Nonetheless, downregulation of both MMPs was not observed in T100 and T1000 groups. In addition, T10 group showed more rapid recovery of hind limb strength compared with T100 and T1000 groups. We propose that the neuroprotective effect of low dose trehalose is mediated by attenuation of MMP-2 and MMP-9 expression.