Optimization Of Formulation Parameters Research Articles

Novel nanoformulation for enhanced amphotericin B efficacy and sustained release using vetiver root cellulose nanofibers against Candida albicans

The formidable antifungal agent, Amphotericin B, is well-known for its potency; however, its clinical application has been significantly limited due to toxicity and poor solubility. This study aims to address these challenges by developing and evaluating a novel nano-cellulose-based formulation of Amphotericin B to enhance its efficacy. Amphotericin B was encapsulated within cellulose nanofibers at varying ratios to optimize formulation parameters, including drug concentration, particle size, zeta potential, and entrapment efficiency. Notably, a composition ratio of 10:1 of cellulose nanofibers to Amphotericin B achieved an impressive encapsulation efficiency of 96.64%. Subsequent physicochemical characterizations employing techniques such as FTIR, DLS, XRD, and SEM provided insights into structural attributes and interactions within formulation. Controlled and extended-release profiles were observed at various physiological pH levels, with the Korsmeyer-Peppas model showing the highest correlation, indicating predominant drug diffusion. Importantly, nanoformulation demonstrated non-toxicity to A431 cells and human erythrocytes up to a maximum concentration of 20 μg/ml, as corroborated by MTT and hemolysis assays. Furthermore, antimicrobial susceptibility and efficacy assessments, conducted using agar disc diffusion and broth micro-dilution methods, revealed enhanced inhibition of Candida albicans growth. The nanoformulation produced a larger diameter of the inhibition zone (DIZ) of 19.66 mm compared to a DIZ of 16.33 mm for Amphotericin B alone. Impressively, the nanoformulation exhibited a minimum inhibitory concentration (MIC) of 25 μg/ml against Candida albicans, underscoring its heightened efficacy. Additionally, the formulation's ability to improve the targetability and bioavailability of Amphotericin B holds promise for enhancing its antifungal effectiveness while reducing associated toxicity.

Synthesis of a Hematite‐Geopolymer Composite: Optimization of Formulation Parameters and Application to the Detection of Pb2+ Ions in Aqueous Solution

AbstractThe Composite Centered Experimental Design (CCED) using the response surface methodology was used to optimize the synthesis of a hematite‐geopolymer composite, applied to the preparation of a Pb2+ electrochemical sensor. Two important experimental parameters in the formulation (curing time and hematite content) were considered in the optimization of the synthesis of the composite material. The electrochemical signal of Pb2+ at a carbon paste electrode modified by the synthesized composite was used as a response to identify the best formulation. After applying the generated experimental plan, the optimal composite material was obtained using 17.08% hematite and a curing time of 0.16 days. The characterization of the optimized composite material revealed the presence of a porous structure and a poly(phospho‐ferro‐siloxo) network, but with a fraction of well dispersed and unreacted hematite. Preliminary experiments confirmed that the sensor prepared with the composite showed high stability and reproducibility of the Pb (II) signal, justifying its application for accurate sensing of the metal cation in an aqueous solution. A Pb2+ calibration curve was obtained after optimizing the experimental detection parameters (composition of the carbon paste electrode, pH of the accumulation solution, accumulation time, and electrolysis potential). A detection limit of 0.2 nM (based on a signal‐to‐noise ratio of 3) was obtained for a studied concentration range between 0.04 and 0.48 nM. The designed sensor also showed remarkable selectivity and excellent performance in real media samples (spring, tap, rain, and well water).

Silk Fibroin Nanofibers: Advancements in Bioactive Dressings through Electrospinning Technology for Diabetic Wound Healing

Background: Non-healing diabetic wounds represent a significant clinical challenge globally, necessitating innovative approaches in drug delivery to enhance wound healing. Understanding the pathogenesis of these wounds is crucial for developing effective treatments. Bioactive dressings and polymeric nanofibers have emerged as promising modalities, with silk biomaterials gaining attention for their unique properties in diabetic wound healing. Purpose of Review: The purpose of this review is to examine the challenges and innovations in treating non-healing diabetic wounds, emphasizing the global burden and the need for effective solutions. This review explores the complex mechanisms of wound healing in diabetes and evaluates the therapeutic potential of bioactive dressings and polymeric nanofibers. Special focus is given to the application of silk biomaterials, particularly silk fibroin, for wound healing, detailing their properties, mechanisms, and clinical translation. This review also describes various nanofiber fabrication methods, especially electrospinning technology, and presents existing evidence on the effectiveness of electrospun silk fibroin formulations. Recent Findings: Recent advancements highlight the potential of silk biomaterials in diabetic wound healing, owing to their biocompatibility, mechanical strength, and controlled drug release properties. Electrospun silk fibroin-based formulations have shown promising results in preclinical and clinical studies, demonstrating accelerated wound closure and tissue regeneration. Summary: Non-healing diabetic wounds present a significant healthcare burden globally, necessitating innovative therapeutic strategies. Bioactive dressings and polymeric nanofibers, particularly silk-based formulations fabricated through electrospinning, offer promising avenues for enhancing diabetic wound healing. Further research is warranted to optimize formulation parameters and validate efficacy in larger clinical trials.

Optimizing gypsum particleboard properties: An orthogonal analysis of pennisetum giganteum and phosphogypsum composites

Gypsum particleboard is attracting attention in the construction industry due to its excellent properties. However, the traditional raw materials for gypsum particleboard are facing a shortage of supply. In this study, we innovatively utilized bulk solid waste Phosphogypsum and Pennisetum giganteum for the first time to manufacture gypsum particleboard. This approach not only effectively addresses the issue of insufficient supply of traditional raw materials for gypsum particleboard but also provides a new pathway for the resource utilization of phosphogypsum. Through an orthogonal experimental design, we focused on optimizing the gypsum particleboard formulation, concentrating on factors such as density, the ratio of Pennisetum giganteum to gypsum (grass-plaster ratio), the ratio of water to gypsum (water-plaster ratio), and the size of the particles. The study determined that the optimal formulation parameters were a density of 1.2 g/cm³, a grass-plaster ratio of 0.20, a water-plaster ratio of 0.25, and a particle mesh number of 14. Under these conditions, the gypsum particleboard exhibited excellent performance, characterized by a static flexural strength of 6.5 MPa, a modulus of elasticity of 2010 MPa, an internal bond strength of 0.4 MPa, a 24-hour water-absorption thickness expansion rate of 2.2%, and an equilibrium moisture content of 1.6%, all meeting the American Society for Testing and Materials (ASTM) Standard D1037. These findings indicate that gypsum particleboards made with Pennisetum giganteum and phosphogypsum can perform comparably to those made with conventional materials. Additionally, a performance prediction model was established using Multiple Linear Regression Analysis (MLRA). The analysis revealed a significant linear relationship between the independent and dependent variables in the model, with the Analysis of Variance (ANOVA) significance levels being less than 0.05, demonstrating statistical significance. This result provides a theoretical basis for the future development of high-performance gypsum particleboard.

Development and Evaluation of Riluzole Loaded PLGA Nanoparticles for Improved Permeability across BBB

Blood-brain barrier is a physiological barrier that prevents drugs from reaching the brain or being bioavailable for treating brain disorders. Degenerative diseases like amyotrophic lateral sclerosis (ALS) seriously impact our daily lives. The Food and Drug Administration (FDA) approved this drug to treat ALS as a chemical derivative of 2- amino-6 [tri-fluoro-methoxy] benzo-thiazole. In order to improve the drug’s therapeutic efficacy, poly-(lactic-co-glycolic acid) nanoparticles (PLGA) were loaded with riluzole and deposited using emulsifying solvent deposition. A design expert software program was used to optimize formulation parameters, including polymer concentration, surfactant concentration, and stirring speed, based on the particle size, zeta potential, and entrapment efficiency responses. Three formulations were taken forward for further study based on the results of 20 trials. Compared to differential scanning calorimetry and fourier transform infrared spectroscopy (FTIR) studies performed beforehand, there were no significant interactions between RZL and the excipients. Nanoparticles prepared with scanning electron microscopy had a smooth surface and a spherical shape. The particle size distribution ranged from 184 ± 74 nm to a maximum of 204.5 ± 71. As a consequence, the particle size distribution is relatively narrow, with lower polymer concentrations, and is ideal for drug delivery. A range of -17.3 to -18.2mV was found for the zeta potential of the nanoparticles. The encapsulation efficiency ranged from 42.61 ± 3.61 to 60.02 ± 1.94%, forming 1:1 to 1:4 drug: Polymer ratios, respectively. Over a period of 22 to 26 hours, the RLZ was continuously released from the nanoparticles. A loading dose may be built by 24% of the drug being released within 3 hours of administration.

Optimization of natural rubber foams: Effect of foaming agent content and processing conditions on the cellular structure and mechanical properties

In the past decades, natural rubber (NR) foams became popular in the automotive, construction and aerospace industries because of their lightweight, flexibility and shock-absorbing properties. The selection of optimal formulation and processing parameters is critical to produce foam with specific properties depending on the application. In this study, the effect of foaming agent concentration, foaming temperature and time on the morphological and mechanical properties of NR foams was investigated. First, increasing the foaming agent content from 5 to 9 phr (parts per hundred rubber) increased the cell size (16%), while decreasing the compression modulus (28%). In the second part, increasing the foaming temperature (145 to 155°C) resulted in larger cell size (163%); while decreasing the cell density (28%), compression modulus (2%), and hardness (1%). In the third part, increasing the foaming time (25 to 45 min) led to smaller cell size (63%) combined with higher cell density (100%), compression modulus (16%), and hardness (3%). Based on all the results obtained, the best NR foam was obtained with 7 phr of foaming agent and produced at 150°C for 35 min leading to superior morphological and mechanical performance: the smallest cell size (25 µm) and the most uniform cell size distribution ( Đ = 1.03) generating the highest compression modulus (3.36 MPa). Finally, the experimental compression results were combined to build a nonlinear regression model to optimize the formulation and processing conditions leading to 6.5 phr of OBSH molded at 150°C for 36 min. The model showed good agreement with a validation test with less than 2% deviation observed for both compression modulus and strength.

PREPARATION OF LIPID NANOCARRIER FORMULATIONS AND CYTOTOXICITY STUDIES OF DONEPEZIL

Objective: Our research endeavors to discover innovative formulations for the pharmaceutical component of radiopharmaceuticals, which are used to diagnose Alzheimer's disease. Our approach involves the incorporation of Donepezil, a proven active ingredient, into lipid-based nanocarrier systems. Additionally, we have conducted a comprehensive study on the cytotoxicity of Donepezil as a vital aspect of our research. Material and Method: Two distinct techniques were employed in creating nanocarrier formulations: emulsion and sonication. Malvern Zeta Sizer measurements were conducted to assess the properties of the prepared formulations. In addition, the cell proliferation kit II (XTT) was used to evaluate the cytotoxicity of the active ingredient Donepezil. Result and Discussion: Formulations with particle sizes ranging from 100-200 nm have been selected based on the results of characterization studies. Cytotoxicity assays have shown that amounts of Donepezil (50, 100, 500, 1000, 2000, and 5000 µg/ml) are biocompatible. These findings confirm the optimal formulation parameters for producing high-quality Donepezil-based pharmaceutical products. The characterization studies of the prepared formulations have shown that they have the potential to be used in the diagnosis of Alzheimer's disease.

Enhancing osteogenic differentiation of dental pulp stem cells through rosuvastatin loaded niosomes optimized by Box-Behnken design and modified by hyaluronan: a novel strategy for improved efficiency

Bone tissue engineering necessitates a stem cell source capable of osteoblast differentiation and mineralized matrix production. Dental pulp stem cells (DPSCs), a subtype of mesenchymal stem cells from human teeth, present such potential but face challenges in osteogenic differentiation. This research introduces an innovative approach to bolster DPSCs’ osteogenic potential using niosomal and hyaluronan modified niosomal systems enriched with rosuvastatin. While rosuvastatin fosters bone formation by regulating bone morphogenetic proteins and osteoblasts, its solubility, permeability, and bioavailability constraints hinder its bone regeneration application. Using a Box-Behnken design, optimal formulation parameters were ascertained. Both niosomes were analyzed for size, polydispersity, zeta potential, and other parameters. They displayed average sizes under 275 nm and entrapment efficiencies exceeding 62%. Notably, niosomes boosted DPSCs’ cell viability and osteogenic marker expression, suggesting enhanced differentiation and bone formation. Conclusively, the study underscores the potential of both niosomal systems in ameliorating DPSCs’ osteogenic differentiation, offering a promising avenue for bone tissue engineering and regeneration.Graphical

Optimizing the formulation variables for encapsulation of linezolid into polycaprolactone inhalable microspheres using double emulsion solvent evaporation

Inhaled antibiotics delivered through dry powder inhalers (DPIs) effectively treat severe bacterial infections by directly targeting the lungs. Our study focused on developing inhalable dry powder microspheres of linezolid (LNZ) using biodegradable polycaprolactone (PCL) polymer. The LNZ-PCL microspheres were fabricated using a double emulsification solvent evaporation method. Optimization of formulation parameters was performed using a factorial design. Evaluation of the microspheres included size, shape, drug loading, entrapment efficiency, aerosolization, and drug release. The morphological analysis confirmed spherical-shaped rough particles within the inhalable size range. The encapsulation efficiency was determined to be 52.84%, indicating successful drug incorporation. Aerosolization efficiency was significantly enhanced when LNZ-PCL microspheres were combined with lactose as a carrier, achieving a fine particle fraction (FPF) value of 70.90%. In-vitro dissolution studies demonstrated sustained drug release for over 24 h under lung pH conditions. Overall, our study highlights the potential of inhalable LNZ-PCL microspheres as a targeted approach for treating pulmonary tuberculosis. Further research and in-vivo studies are needed to validate their effectiveness in life-threatening bacterial infections.

Application of statistical tools for the formulation and optimization of carvedilol mucoadhesive buccal films by using natural polymers

The aim and objective of this study was to create mucoadhesive buccal films that contained the multipurpose medical carvedilol, which has a variety of medicinal uses. Materials and methods. The films were equipped using a solvent casting technique and concentrations of natural polymers, including Sweet basil, Lime Basil seeds and Purple basil mucilage. The influence of Carbopol 934 P, a selected natural polymer, was also investigated. The formulation variables were improved by the use of a factorial design of experiments and evaluated for their physico-chemical and in vitro evaluations. Result. These evaluations provided crucial insights into the properties of the buccal films. To evaluate the release profile and release kinetics of carvedilol from the films, in vitro drug release experiments were carried out in a phosphate buffer solution. Ex vivo permeation tests using fresh sheep buccal mucosa were performed to evaluate the drug's permeation through the buccal membrane. Samples were taken at regular intervals, and a UV Spectrophotometer was used for analysis. With a polymer solution concentration at level "3," formulation run R20 showed the best optimized buccal formulation. This formulation shows promise for further in vivo research. Conclusions. The results of this study offer important new evidence about the design and efficacy of mucoadhesive buccal films containing carvedilol. The optimization of formulation parameters and the assessment of physicochemical properties and drug release kinetics contribute to the progress of reproducible buccal films

Pluronic F-127 Hydrogel for Delivering Antimicrobial Agents: A Bibliometric Analysis using Scopus Database

Infectious diseases caused by pathogenic microorganisms pose significant threats to public health globally. The emergence of antibiotic-resistant bacteria has further complicated the treatment of these infections, necessitating the exploration of alternative therapeutic strategies. Among these strategies, the use of hydrogels as delivery systems for delivering antimicrobial agents has gained considerable attention. This paper presents a comprehensive bibliometric analysis of the utilization of Pluronic F-127 (PF-127) hydrogel for delivering antimicrobial agents. The aim of this study is to explore the current research landscape, identify key trends, influential authors, and prominent journals in this field. The analysis is based on a systematic search conducted using the Scopus database. The analysis covered publication trends, geographic distribution, influential authors, and key journals in the field of PF-127 hydrogel-based antimicrobial agent delivery. The results revealed the growing interest in this field, with a focus on countries such as India, the United States, and Egypt. The analysis also identified top authors, institutions, and journals contributing to the research. The findings reveal the growth of research in this area, highlighting the potential of PF-127 hydrogel as a promising vehicle for antimicrobial agent delivery. It highlights the need for further research to optimize formulation parameters, explore combination therapies, conduct in vivo studies, and promote collaboration to maximize the therapeutic potential of PF-127 hydrogel-based delivery systems in combating infectious diseases and antimicrobial resistance. This paper provides valuable insights into the existing literature and serves as a reference for future research and development in the field.

Highly stable nanostructured lipid carriers containing candelilla wax for d-limonene encapsulation: Preparation, characterization and antifungal activity

The objective of this work was to develop nanostructured lipid carriers (NLCs) with preservation effect by using pea protein isolate (PPI) nanoparticles as emulsifiers, candelilla wax (CW) as organo-gelator and d-limonene (DL) as antifungal agent. The optimal formulation parameters of NLCs were firstly determined based on results of particle size, poly-dispersity index and zeta potential, and then NLCs prepared by optimal formulation were further characterized. The results showed that DL was successfully encapsulated inside NLCs. Moreover, the encapsulation of amorphous DL led to more disordered crystalline state of NLCs. In addition, in comparing the properties of NLCs and nanoemulsions (NEs) without CW, it was found that the addition of CW seemed to have several beneficial effects on NLCs: 1) NLC droplets were well dispersed, whereas NE droplets exhibited coalescence and flocculation; 2) compared with NEs, NLCs displayed excellent storage stability and inhibition ability of DL release. Furthermore, antifungal activity of NLCs was observed by in vitro and in vivo study. The acquired information in current research can provide novel insight into development of stable and antifungal nanocarriers that own a promising application in tomato preservation.

Induction of Bleb Structures in Lipid Nanoparticle Formulations of mRNA Leads to Improved Transfection Potency.

The transfection potency of lipid nanoparticle (LNP) mRNA systems is critically dependent on the ionizable cationic lipid component. LNP mRNA systems composed of optimized ionizable lipids often display distinctive mRNA-rich "bleb" structures. Here, it is shown that such structures can also be induced for LNPs containing nominally less active ionizable lipids by formulating them in the presence of high concentrations of pH 4 buffers such as sodium citrate, leading to improved transfection potencies both in vitro and in vivo. Induction of bleb structure and improved potency is dependent on the type of pH 4 buffer employed, with LNP mRNA systems prepared using 300 mm sodium citrate buffer displaying maximum transfection. The improved transfection potencies of LNP mRNA systems displaying bleb structure can be attributed, at least in part, to enhanced integrity of the encapsulated mRNA. It is concluded that enhanced transfection can be achieved by optimizing formulation parameters to improve mRNA stability and that optimization of ionizable lipids to achieve enhanced potency may well lead to improvements in mRNA integrity through formation of the bleb structure rather than enhanced intracellular delivery.

Study and optimization of formulation parameters during freeze–drying cycles of model probiotic: Morphology characterization of lyophilisates by scanning electron microscopy

These experimental data are concerning the optimization of freeze-drying cycles of a model-type Casei probiotic bacteria with water based formulations using lactose and polymer polyvinylpyrrolidone (PVP) as cryo-/lyo-protectants. After a previous study devoted to the influence of the main freeze-drying parameters (freezing rates; shelf temperature; absolute pressure) on the bacteria survival ratios, this paper reports some morphological data obtained by scanning electron microscopy (SEM) with the final lyophilisates. The numerous and original SEM images realized with different formulations of water binary or ternary mixtures with fixed operating conditions proved to be very useful to explain and to understand the different bacteria survival ratios observed. Thus, with bacteria or micro-organisms systems, this powerful investigation method of characterization of lyophilisates morphology should be more largely used in the future for setting up the optimal formulations parameters (composition) and the connected operating physical parameters of freeze-drying steps (freezing rate, shelf temperature, absolute pressure).

Optimization of Formulation Parameters in Preparation of Fructus ligustri lucidi Dropping Pills by Solid Dispersion Using 23 Full Experimental Design.

Oleanolic acid (OA) is an active ingredient of the traditional Chinese medicine (TCM) Fructus ligustri lucidi (FLL). Its clinical use is restricted because it is water-insoluble and has limited dosage forms of administration at present. Hence, the FFL dropping pills were prepared by the hot-melt method of solid dispersion technology. A 23 factorial design was used to examine the effects of the materials used to prepare the dropping pills (e.g., different ratios of PEG4000 and PEG6000, FLL extract loading, and percentage of Tween 80) on parameters such as dropping pill roundness, weight variation, and disintegration time. Moreover, 23 full factorial design was utilized to search for the optimal formulation for dissolution experiments. The results showed that the percentage of Tween 80 demonstrated significant effects on dropping pill roundness, weight variation, and disintegration time; FLL extract loading affected roundness and weight variation; and different ratios of PEG4000 and PEG6000 only affected disintegration time. The optimal formulation of the dropping pills released 70% of the drug after 30 min of dissolution release, which was faster than commercially available FLL Chinese medicines. Furthermore, the amount released was higher than that of commercially available formulations. In this study, a solid dispersion technique was used to successfully produce FLL dropping pills. In addition to improving the water insolubility of FLL and increasing the dissolution release percentage of the drug, we increased the application value of FLL and reduced the issues of traditional administration dosage forms.

Intracellular delivery of messenger RNA to macrophages with surfactant-derived lipid nanoparticles

The broad biomedical applications of messenger RNA (mRNA)-based therapeutics rely heavily on the rapid development of mRNA delivery systems. In this study, dual-component lipid nanoparticles (LNPs) were developed for intracellular delivery of mRNA to macrophages. By screening a panel of quaternary ammonium compounds with varying alkyl or aryl side chains, a cationic surfactant containing two hexadecyl tails was found to be effective for mRNA delivery with the assistance of fusogenic lipids. Further investigating structure alterations and optimization of formulation parameters, we found that a surfactant-derived ionizable lipid mixed with a fusogenic lipid was capable of condensing mRNA and self-assembling into LNPs. Without using the PEGylated lipid, the resulting LNPs were able to render the exogenous mRNA resistant to hydrolysis by nucleases and displayed excellent biocompatibility, along with the capacity to deliver mRNA to hard-to-transfect. Overall, the dual-component nanocarrier provides a novel mRNA delivery platform for genetic engineering of macrophages.

In vivo assessment of triazine lipid nanoparticles as transfection agents for plasmid DNA.

Non-viral vectors for in vivo delivery of plasmid DNA rely on optimized formulations to achieve robust transgene expression. Several cationic lipids have been developed to deliver nucleic acids, but most recent literature has focused on mRNA due to its increased expression profile and excluded plasmid DNA, which may have the advantage of being less immunogenic. In this study, we describe the in vivo evaluation of cationic triazine based lipids, previously prepared by our group. We identify one lipid with limited in vivo toxicity for studies to optimize the lipid formulations, which include an evaluation of the influence of PEG and helper lipids on transgene expression. We then demonstrate that lipoplexes, but not lipid nanoparticles, formed from triazine lipids achieve similar transgene expression levels as AAV vectors and offer enhanced expression as compared to a commercially available cationic lipid, DOTAP. Importantly, the lipid nanoparticles and lipoplexes induce minimal antibody profiles toward the expressed protein, while serving as a platform to induce robust antibody responses when directly delivering the protein. Collectively, these data demonstrate the potential for triazine based lipids as non-viral vectors for gene delivery, and highlights the need to optimize each formulation based on the exact contents to achieve enhanced transgene expression with plasmid DNA constructs.

Multivesicular liposomal depot system for sustained delivery of risperidone: Development, characterization, and toxicity assessment

Objective Considering the limitations of conventional risperidone (RSP) therapies, the present research characterizes the usefulness of multivesicular liposomes (MVLs) as an efficient controlled-release carrier for this widely used antipsychotic drug, to be employed for the treatment of schizophrenia. Methods A 23 full factorial design based on three independent variables was implemented to plan the experiments: the molar ratios of lipid to the drug, triolein to phospholipid, and cholesterol to phospholipid. The impacts of these parameters on the risperidone encapsulation efficiency and its release pattern within the first 24 and 48 h were investigated as dependent variables. Then, the optimized liposomal system was further in-depth analyzed in terms of size, morphological and structural features, release profile over 15 days, biocompatibility, and stability. Results Optimized formulation parameters gave rise to MVLs possessing a spherical morphology with a median diameter of about 8 μm, a relatively narrow size distribution, and encapsulation efficiency of 57.6%. These carriers not only exhibited a sustained-release behavior in vitro, lasting until the end of the 15 days, but also underwent a negligible change in their size and RSP incorporation over two months at refrigerator condition. Furthermore, in vitro cytotoxicity and hemolysis assessments revealed that the optimized MVL formulation is biocompatible. Conclusion This study revealed the potential of MVLs as a promising system for the delivery of RSP and could open a new vista for the successful management of schizophrenia.

Optimization and evaluation of propolis liposomes as a promising therapeutic approach for COVID-19.

The present work aimed to develop an optimized liposomal formulation for enhancing the anti-viral activity of propolis against COVID-19. Docking studies were performed for certain components of Egyptian Propolis using Avigan, Hydroxychloroquine and Remdesivir as standard antivirals against both COVID-19 3CL-protease and S1 spike protein. Response surface methodology and modified injection method were implemented to maximize the entrapment efficiency and release of the liposomal formulation. The optimized formulation parameters were as follow: LMC of 60mM, CH% of 20% and DL of 5mg/ml. At those values the E.E% and released % were 70.112% and 81.801%, respectively with nanosized particles (117±11nm). Docking studies revealed that Rutin and Caffeic acid phenethyl ester showed the highest affinity to both targets. Results showed a significant inhibitory effect of the optimized liposomal formula of Propolis against COVID-3CL protease (IC50=1.183±0.06) compared with the Egyptian propolis extract (IC50=2.452±0.11), P<0.001. Interestingly, the inhibition of viral replication of COVID-19 determined by RT_PCR has been significantly enhanced via encapsulation of propolis extract within the liposomal formulation (P<0.0001) and was comparable to the viral inhibitory effect of the potent antiviral (remdesivir). These findings identified the potential of propolis liposomes as a promising treatment approach against COVID-19.

Optimization and Evaluation of Poly(lactide-co-glycolide) Nanoparticles for Enhanced Cellular Uptake and Efficacy of Paclitaxel in the Treatment of Head and Neck Cancer.

The particle size (PS) and encapsulation efficiency (EE%) of drug-loaded nanoparticles (NPs) may inhibit their cellular uptake and lead to possible leakage of the drug into the systemic circulation at the tumor site. In this work, ultra-high paclitaxel-loaded poly(lactide-co-glycolide) NPs (PTX-PLGA-NPs) with ultra-small sizes were prepared and optimized by adopting the principles of quality by design (QbD) approach. The optimized PTX-PLGA-NPs showed ultra-small spherical particles of about 53 nm with EE% exceeding 90%, a relatively low polydispersity index (PDI) of 0.221, an effective surface charge of −10.1 mV, and a 10-fold increase in the in vitro drug release over 72 h relative to free drug. The cellular viability of pharynx carcinoma cells decreased by almost 50% in 24 h following treatment with optimized PTX-PLGA-NPs, compared to only 20% from the free drug. The intracellular uptake of PTX-PLGA-NPs was highly favored, and the antitumor activity of PTX was remarkably improved with a reduction in its half maximal inhibitory concentration (IC50), by almost 50% relative to free drug solution. These results suggest that the optimal critical formulation parameters, guided by QbD principles, could produce PLGA-NPs with remarkably high EE% and ultra-small PS, resulting in enhanced cellular uptake and efficacy of PTX.