Overcoming biological barriers with block copolymers-based self-assembled nanocarriers. Recent advances in delivery of anticancer therapeutics

Cancer is one of the most common life-threatening illness and it is the world’s second largest cause of death. Chemotherapeutic anticancer drugs have many disadvantages, which led to the need to develop novel strategies to overcome these shortcomings. Moreover, tumors are heterogenous in nature and there are various biological barriers that assist in treatment reisistance. In this sense, nanotechnology has provided new strategies for delivery of anticancer therapeutics. Recently, delivery platforms for overcoming biological barriers raised by tumor cells and tumor-bearing hosts have been reported. Among them, amphiphilic block copolymers (ABC)-based self-assembled nanocarriers have attracted researchers worldwide owing to their unique properties. In this work, we addressed different biological barriers for effective cancer treatment along with several strategies to overcome them by using ABC‐based self-assembled nanostructures, with special emphasis in those that have the ability to act as responsive nanocarriers to internal or external environmental clues to trigger release of the payload. These nanocarriers have shown promising properties to revolutionize cancer treatment and diagnosis, but there are still challenges for their successful translation to clinical applications.Fil: Torres, Jazmin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Dhas, Namdev. Nirma University. Institute Of Pharmacy; IndiaFil: Longhi, Marcela Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: García, Mónica Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentin

Co-rotating twin screw process for continuous manufacturing of solid crystal suspension: A promising strategy to enhance the solubility, permeation and oral bioavailability of Carvedilol [version 3; peer review: 1 approved, 2 approved with reservations]

Background In the current work, co-rotating twin-screw processor (TSP) was utilized to formulate solid crystal suspension (SCS) of carvedilol (CAR) for enhancing its solubility, dissolution rate, permeation and bioavailability using mannitol as a hydrophilic carrier. Methods In-silico molecular dynamics (MD) studies were done to simulate the interaction of CAR with mannitol at different kneading zone temperatures (KZT). Based on these studies, the optimal CAR: mannitol ratios and the kneading zone temperatures for CAR solubility enhancement were assessed. The CAR-SCS was optimized utilizing Design-of-Experiments (DoE) methodology using the Box-Behnken design. Saturation solubility studies and in vitro dissolution studies were performed for all the formulations. Physicochemical characterization was performed using differential scanning calorimetry , Fourier transform infrared spectroscopy, X-ray diffraction studies, and Raman spectroscopy analysis. Ex vivo permeation studies and in vivo pharmacokinetic studies for the CAR-SCS were performed. Stability studies were performed for the DoE-optimized CAR-SCS at accelerated stability conditions at 40 ºC/ 75% RH for three months. Results Experimentally, the formulation with CAR: mannitol ratio of 20:80, prepared using a KZT of 120 ºC at 100 rpm screw speed showed the highest solubility enhancement accounting for 50-fold compared to the plain CAR. Physicochemical characterization confirmed the crystalline state of DoE-optimized CAR-SCS. In-vitro dissolution studies indicated a 6.03-fold and 3.40-fold enhancement in the dissolution rate of optimized CAR-SCS in pH 1.2 HCl solution and phosphate buffer pH 6.8, respectively, as compared to the pure CAR. The enhanced efficacy of the optimized CAR-SCS was indicated in the ex vivo and in vivo pharmacokinetic studies wherein the apparent permeability was enhanced 1.84-fold and bioavailability enhanced 1.50-folds compared to the plain CAR. The stability studies showed good stability concerning the drug content. Conclusions TSP technology could be utilized to enhance the solubility, bioavailability and permeation of poor soluble CAR by preparing the SCS

Overcoming Biological Barriers With Block Copolymers-Based Self-Assembled Nanocarriers. Recent Advances in Delivery of Anticancer Therapeutics

Cancer is one of the most common life-threatening illness and it is the world’s second largest cause of death. Chemotherapeutic anticancer drugs have many disadvantages, which led to the need to develop novel strategies to overcome these shortcomings. Moreover, tumors are heterogenous in nature and there are various biological barriers that assist in treatment reisistance. In this sense, nanotechnology has provided new strategies for delivery of anticancer therapeutics. Recently, delivery platforms for overcoming biological barriers raised by tumor cells and tumor-bearing hosts have been reported. Among them, amphiphilic block copolymers (ABC)-based self-assembled nanocarriers have attracted researchers worldwide owing to their unique properties. In this work, we addressed different biological barriers for effective cancer treatment along with several strategies to overcome them by using ABC‐based self-assembled nanostructures, with special emphasis in those that have the ability to act as responsive nanocarriers to internal or external environmental clues to trigger release of the payload. These nanocarriers have shown promising properties to revolutionize cancer treatment and diagnosis, but there are still challenges for their successful translation to clinical applications.</jats:p

BOX-BEHNKEN DESIGN-BASED DEVELOPMENT OF ECO-FRIENDLY RP-HPLC ANALYTICAL METHOD FOR THE QUANTIFICATION OF ERASTIN FROM THE MESOPOROUS SILICA NANOPARTICLES

Objective: Globally, cancer remains a major source of illness and mortality. Approximately 30% of initial glioblastomas and 80% of all malignant ones are gliomas. Erastin (ERT) is a small molecule that kills cancer cells through ferroptosis and treats brain cancer. The current work aims to optimize, establish, and validate a High-Performance Liquid Chromatography (HPLC) method with sufficient sensitivity and specificity to measure ERT in Mesoporous Silica Nanoparticles (MSNs). The HPLC method was optimized using the Design of Experiments (DoE) technique. The novelty of this project is the development of the DoE-based HPLC method for quantifying ERT from the MSNs. Methods: The Box-Behnken Design (BBD) was used for the method optimization, and buffer ratio, injection volume, buffer pH, and flow rate were used as the independent factors. The dependent variables were retention time (RT) of ERT, peak area of ERT, and tailing factor (TF) of ERT. The optimized chromatographic conditions were: buffer ratio of 80%, buffer pH 3.8, flow rate 0.9 mL/min, and injection volume 8 µL. The established HPLC method was validated as per international council for harmonisation (ICH) Q2 (R1) recommendations. Results: The optimization of the HPLC method was done using BBD, and the desirability value was found to be 0.992. The established method showed good linearity (R2 = 0.9991) with a 12-500 ng/mL range, and LOD and LOQ were 2.71 ng and 6.25 ng, respectively. The Mesoporous Silica Nanoparticle (MSNs) matrix did not affect the specificity of our validated HPLC method for the analysis of ERT. Analysing the formulation's surface morphology helped confirm the synthesized MSNs. The proposed HPLC method was effectively used to calculate the medication loaded in the MSNs and to measure the amount of ERT entrapped. The % entrapment efficiency (EE) for ERT in MSNs was found to be 76.07±2.56%, and the % drug loading (DL) for ERT in MSNs was found to be 14±1.87%. The established HPLC method for estimating ERT was found to be environmentally friendly with an overall analytical greenness  (AGREE) score of 0.6. Conclusion: The established HPLC method was developed, optimized, and validated as per ICH Q2 R1 guidelines. The HPLC method was found to be eco-friendly as per the AGREE analysis