Production of Nano-Composite Artificial Bone Tissue Using Bioceramic Synthesis from Bio-Waste
Certain specially structured ceramics, which can be used as biomaterials to replace bone, have recently started being utilized in the medical field. The aim of this study is to produce high-bioactivity silica from corn cob waste, a widely available organic material in nature, and combine it with calcium oxide (CaO) obtained by grinding organic mussel shell waste with high bioactivity. This combination is intended to synthesize dicalcium silicate (2CaO.SiO₂) to develop an alternative tissue scaffold with high bioactivity, capable of replacing bone, for existing titanium alloys. The goal is to incorporate this scaffold into PEEK (polyether ether ketone), a novel tissue scaffold material, at varying percentages to create a next-generation innovative bone substitute material. An additional objective is to demonstrate through biocompatibility tests that the produced ceramic-polymer biocomposite exhibits antibacterial activity against Staphylococcus aureus.
Natural resources utilization for the in-house production of fluorescence lipid nanoparticles
Nanotechnology, a transformative force, has steadily gained traction across multiple scientific disciplines, including physics, chemistry, engineering, and biology. It offers unprecedented capabilities, especially in the realm of nanoscale particles, ushering in new paradigms in various applications. One of the most revolutionary applications of nanotechnology is in the pharmaceutical sector. Here, nanoparticles have transformed drug and vaccine delivery systems, offering both efficacy and precision. Among these nanoparticles, lipid nanoparticles (LNPs) have stood out, especially for their role in delivering nucleic acid-based drugs and vaccines. These LNPs are intricate assemblies composed of lipids and nucleic acid complexes, offering an amalgamation of stability and deliverability. Such properties have rendered LNPs as invaluable tools in enhancing therapeutic efficacy while minimizing off-target side effects. The myriad of nanoparticles available includes the likes of silver, gold, and lipid nanoparticles. However, the emphasis of this research lies with lipid nanoparticles, given their widespread success in the pharmaceutical arena. LNPs have showcased their potential in delivering drugs with low therapeutic indices, emphasizing their capability to act as versatile platforms for novel drug development. Recent advances have further expanded the horizons of LNPs, paving the way for novel antisense oligonucleotides, innovative vaccines, and complex lipid nanoparticle formations. Characterizing these nanoparticles is paramount, not only for the development of novel drugs but also to comprehend their in vivo behavior. Their multifaceted nature, stemming from their unique excipients, core-bilayer design, and varying sizes, makes their characterization a critical step in the research and development pipeline.
In silico Investigation of Cyclosporine Conjugates as Potential Anti-angiogenic Agents via NFAT Inhibition
Calcineurin (CN) activation is a main cause of cancerous tumor formation, one of the leading causes of death globally. Cyclosporine-A (CsA) is a commercially available oral drug that inhibits CN activation; however, low bioavailability limits its use. Nine patented CsA conjugates are potential alternatives to CsA as they have improved cytotoxicities and bioavailabilities but unknown CN-binding affinity. This study aimed to identify the CNinhibition strength and bioavailability of CsA conjugates in silico drug-likeness evaluation via modified Lipinski’s Rule of Five was done on CsA, voclosporin, and CsA conjugates to test bioavailability. The binding affinities of bioavailable compounds were computed via docking to CN in five trials, and the binding affinities were compared. The Water-soluble, RVal, IIA, Alpha, and MeBmt 2 conjugates showed improved bioavailabilities compared to CsA as they passed the drug-likeness screening. After five trials of computational docking to CN, the IIA and RVal conjugates showed improved binding affinities at -15.8 kcal/mol and -15.2 kcal/mol, respectively, compared to CsA at -14.3 kcal/mol. Notably, IIA also showed an improved binding affinity compared to voclosporin at -15.5 kcal/mol. These results suggest that CsA conjugates may be better oral chemotherapeutic drugs than CsA.
Eradicating Cystic Fibrosis Biofilms by a Novel Non-Toxic, Multi-Pathway Salicylate Therapy
1.1. Cystic Fibrosis Biofilms Biofilms are bacterial aggregates in a matrix of polysaccharides, proteins and nucleic acids (Donlan, 2002). They account for 80% of all chronic infections and cause over 500,000 deaths annually. Cystic fibrosis (CF) is a genetic disorder characterized by mucus accumulation in the respiratory tracts (Morrison et al., 2020). This impairs mucociliary clearance, allowing chronic colonization by bacterial biofilms, leading to fatal respiratory failure, lung scarring, and necrosis of pulmonary epithelial tissues (Martin et al., 2021). 1.2. Obstacles in Current Treatments Three major therapies are used against CF biofilms: (1) aminoglycoside antibiotics like tobramycin, (2)non-aminoglycoside antibiotics such as ciprofloxacin and vancomycin, and (3) non-antibiotic therapies including flushing, chlorination, and ultraviolet disinfection. These have two major flaws. First, they are cytotoxic; 30% of patients experience acute kidney injury after three days of intravenous aminoglycoside therapy (Joyce et al., 2017). Furthermore, non-aminoglycoside therapies can cause phospholipid buildup in lysosomes of proximal tubule epithelial cells, accounting for 10-20% of acute renal failure cases. Second, antibiotic resistance due to horizontal gene transfer and mutations has significantly reduced treatment effectiveness. Therefore, cystic fibrosis biofilms remain a critical threat with few effective treatments. 1.3. Salicylate Derivatives This project tackled this issue using an innovative non-antibiotic approach with salicylate derivatives. Salicylates, a class of benzoic acids—benzene-based carboxylic acids (Figure 1)—used in painkillers and blood thinners, were investigated for their antibiofilm potential through a 3-step process: 1. Literature review: Identified three key biofilm therapeutic targets: quorum sensing, bacterial adhesion, and cell motility. Disrupting these pathways would result in biofilm eradication. 2. Molecule Identification: Recognized key molecules in each pathway: LasR, adhesins, and flagellin. Inhibiting these molecules would disrupt the pathways. 3. Screening: Found that salicylates could inhibit the identified molecules, though they had never been tested against cystic fibrosis biofilms.
Trojan Horses in the Fight against Skin Cancer
In photodynamic therapy (PDT), reactive oxygen species are generated within the cytoplasm to destroy cancer cells selectively. Using porphyrinic structures (PS) as photosensitizers holds promise for targeting cancer cells. However, direct incorporation of the porphyrins into cancer cells remains elusive. Hence, Dr. Martina Vermathen’s research introduced specific membranous phospholipid nanocarriers for topical porphyrin applications. However, since a sufficiently high enough concentration of PS in cancer cells has not yet been achieved, this study aimed to improve skin uptake of the nanocarriers. Two approaches were examined: (1) comparing polar and nonpolar porphyrins and (2) assessing the effect of a penetration enhancer, DMSO, through a neat and diluted application. The polarity of the porphyrins was first quantified with a log P test. The nanocarriers were assembled by incorporating two different PS compounds, either the mono- or tetra-4-carboxy substituted phenyl porphyrin. They were then characterized by 1D and 2D-NMR analysis. The porphyrin permeation was tested by Franz diffusion tests on pig ear skin. For the second approach, DMSO was added in the Franz diffusion test, either directly applied on the skin (“neat“) or diluted in the nanocarriers (“diluted”). The log P test for the mono- and the tetra-carboxyphenyl porphyrin resulted in values of 4.5 and -1.1, respectively. The more polar tetra-carboxyphenyl porphyrin exhibited 2.8 times better skin uptake compared to the mono-carboxyphenyl porphyrin. The neat DMSO application increased uptake by a factor of 5.5. The diluted DMSO application worsened skin uptake slightly. Analytical techniques revealed differences in porphyrin encapsulation: The mono-carboxyphenyl porphyrins were encapsulated in the centre, whereas tetra-carboxyphenyl porphyrins were localised around the nanocarriers. Results indicated potential instability of the nanocarriers. The more polar tetra-substituted porphyrins showed superior skin diffusion than the mono-substituted derivative. The neat DMSO application facilitated enhanced skin uptake by inducing membrane destabilization and pore formation but may have limited applicability. Further research is suggested to explore porphyrinic PS with alternative polar substitution patterns and tailored penetration enhancers for lipid-based delivery systems. Overall, the study underscores the importance of molecular properties of the PS system and demonstrates the potential of penetration enhancers in optimizing PDT for skin cancer treatment.
Utilizing Flavonoids From the Invasive Species Pilea Melastomoides and Daucus Carota as Well as the Protein PTK-2 to Create a Skin Gel Aimed for Burn Wound Healing.
Burns are a major global health concern especially in developing countries like 印尼, where southeast asian women experience the highest burn incidents globally. Burns can cause severe physical and psychological impacts, with treatments that are critical to reduce complications. This study focuses on the development of organic, cost-effective burn gels using flavonoid compounds which are Quercetin and Myrecetin which are taken from pilea melastomoides leaves, a wild 印尼n plant and carrot (Daucus Carota). These skin extracts aim to accelerate wound healing, minimize pain and prevent infection. The gel formation involves extracting active compounds using 96% ethanol as it has been effectively used for extracting a wide range of bioactive compounds to preserve their quality by preventing microbial contamination, and ensures a high yield of active ingredients suitable for topical applications. Then it goes through a process of Phytochemical screening to confirm the presence of flavonoids by using the Shinoda test. The formulation process included dissolving the HPC-m (Hydroxypropyl Cellulose) as a gelling agent, then adding plant extracts (pilea melastomoides leaves and carrot), as well as combining other ingredients such as propylene glycol, sodium benzoate, sodium metabisulfite, and disodium EDTA. The gel was stirred thoroughly to ensure uniformity and left at room temperature for 48 hours to attain the required consistency. The gel that was formatted went under various quality assessments, first being organoleptic testing. This test is used to evaluate its physical characteristics which includes color aroma, and consistency which confirms a stable dark green appearance and a natural strong scent from the plant extracts. The homogeneity test is used to verify the uniformity distribution of active compounds across the gel, to ensure a consistent efficacy. The pH test showed the gel’s acidity level which remained the safe range for skin application. Additionally, the spreading ability test demonstrated the gel’s excellent application properties, with consistent results across trials. Subsequently, the in silico analysis was conducted to predict the behaviour of specific flavonoid compounds used which is the myricetin and quercetin, highlighting their potential anti-inflammatory and antimicrobial activities. Further bacterial contamination tests confirmed the gel’s antimicrobial efficacy, reducing the risk of infection in wounds. This study demonstrates that the gel, formulated with pilea melastomoides leaves and carrot skin extracts, effectively utilizes flavonoids and other phytochemicals to reduce inflammation, promote tissue regeneration and retain moisture, which fosters an optimal condition for wound healing. This organic and sustainable burn treatment utilizes locally sourced ingredients, providing a natural solution that speeds up recovery, reduces pain and prevents infections. The results highlight its significant potential for wider healthcare use, especially in resource-limited environments.