A novel chromone-based as a potential inhibitor of ULK1 that modulates autophagy and induces apoptosis in colon cancer.

Aim: Chromones are promising for anticancer drug development.Methods & results: 12 chromone-based compounds were synthesized and tested against cancer cell lines. Compound 8 showed the highest cytotoxicity (LC50 3.2 µM) against colorectal cancer cells, surpassing 5-fluorouracil (LC50 4.2 µM). It suppressed colony formation, induced cell cycle arrest and triggered apoptotic cell death, confirmed by staining and apoptosis markers. Cell death was accompanied by enhanced reactive oxygen species formation and modulation of the autophagic machinery (autophagy marker light chain 3B (LC3B); adenosine monophosphate-activated protein kinase (AMPK); protein kinase B (PKB); UNC-51-like kinase (ULK)-1; and ULK2). Molecular docking and dynamic simulations revealed that compound 8 directly binds to ULK1.Conclusion: Compound 8 is a promising lead for autophagy-modulating anti-colon cancer drugs.

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Non-lamellar lyotropic liquid crystalline nanoparticles as nanocarriers for enhanced drug encapsulation of atorvastatin calcium and proanthocyanidins.

Atorvastatin calcium (ATV) and proanthocyanidins (PAC) have a strong antioxidant activity, that can benefit to reduce the atherosclerotic plaque progression. Unfortunately, the bioavailability of ATV is greatly reduced due to its limited drug solubility while the PAC drug is unstable upon exposure to the atmospheric oxygen. Herein, the lyotropic liquid crystalline nanoparticles (LLCNPs) constructed by a binary mixture of soy phosphatidylcholine (SPC) and citric acid ester of monoglyceride (citrem) at different weight ratios were used to encapsulate the hydrophobic ATV and hydrophilic PAC. The LLCNPs were further characterized by small-angle X-ray scattering and dynamic light scattering. Depending on the lipid composition, the systems have a size range of 140-190 nm and were able to encapsulate both drugs in the range of 90-100%. Upon increasing the citrem content of drug-loaded LLCNPs, the hexosomes (H2) was completely transformed to an emulsified inverse micellar (L2). The optimum encapsulation efficiency (EE) of ATV and PAC were obtained in citrem/SPC weight ratio 4:1 (L2) and 1:1 (H2), respectively. There was a substantial change in the mean size and PDI of the nanoparticles upon 30 days of storage with the ATV-loaded LLCNPs exhibiting greater colloidal instability than PAC-loaded LLCNPs. The biphasic released pattern (burst released at the initial stage followed by the sustained released at the later stage) was perceived in ATV formulation, while the burst drug released pattern was observed in PAC formulations that could be attributed by its internal H2 structure. Interestingly, the cytokine studies showed that the PAC-LLCNPs promisingly up regulate the expressions of tumor necrosis factor-alpha (TNF-α) better than the drug-free and ATV-loaded LLCNPs samples. The structural tunability of citrem/SPC nanoparticles and their effect on physicochemical characteristic, biological activities and potential as an alternative drug delivery platform in the treatment of atherosclerosis are discussed.

Hydrophobic Drug Carrier from Polycaprolactone-b-Poly(Ethylene Glycol) Star-Shaped Polymers Hydrogel Blend as Potential for Wound Healing Application.

Blending hydrogel with an amphiphilic polymer can increase the hydrophobic drug loading and entrapment efficiency of hydrogel-based formulations. In this study, a hydrogel formulation with star-shaped polycaprolactone-b-poly(ethylene glycol) (PCL-b-PEG) as the hydrophobic drug cargo is produced. The 4-arm and 6-arm star-shaped PCL are synthesized with different molecular weights (5000, 10,000, 15,000 g/mol) via ROP and MPEG as the hydrophilic segment is attached via the Steglich esterification. FTIR and 1H-NMR analysis showed the presence of all functional groups for homopolymers and copolymers. Mn for all synthesized polymers is close to the theoretical value while GPC spectra showed a monomodal peak with narrow molecular weight distribution (PDI:1.01-1.25). The thermal degradation temperature and crystalline melting point of synthesized polymers increase with the increase in molecular weight and number of arms. All formulations possess high drug loading and entrapment efficiency (>99%) and increase with increasing molecular weight, number of arms, and amount of polymer in the formulations. All formulations showed a sustained drug release pattern with no initial burst, which follows the Korsmeyer-Peppas kinetic model. The polymer hydrogel formulations showed antibacterial activity against E. coli and S. aureus. The hydrogel containing 4-arm PCL15k-PEG is chosen as the best formulation due to its high drug release, good antimicrobial activity, and morphology.

PEGylated liposomes enhance the effect of cytotoxic drug: A review.

Cancer is a second leading disease-causing death worldwide that will continuously grow as much as 70% in the next 20 years. Chemotherapy is still becoming a choice for cancer treatment despite its severity of side effects and low success rate due to ineffective delivery of the chemodrugs. Since it was introduced in 1960, significant progress has been achieved in the use of liposomes in drug delivery. The study aims to review relevant literatures on role of PEGylated liposome in enhancing cytotoxic activity of several agents. A systematic literature on the use of PEGylated liposomes in anticancer research via Scopus, Google scholar and PubMed databases was conducted for studies published from 2000 to 2022. A total of 15 articles were selected and reviewed from 312 articles identified covering a variety of anticancer treatments by using PEGylated liposomes. PEGylated liposome which is purposed to achieve steric equilibrium is one of enhanced strategies to deliver anticancer drugs. It has been shown that some improvement of delivery and protection form a harsh gastric environment of several anticancer drugs when they are formulated in a PEGylated liposome. One of the successful drugs that has been clinically used is Doxil®, followed by some other drugs in the pipeline Various drugs (compounds) had been used to enhance the efficacy of PEGylated liposomes for targeted cancer cells in vitro and in vivo. In conclusion, PEGylated liposomes enhance drug activities and have great potential to become efficient anticancer delivery to follow Doxil® in the clinical setting.

Gelatin-based hemostatic agents for medical and dental application at a glance: A narrative literature review.

Uncontrolled bleeding is linked to higher treatment costs, risk of post-surgical infection and increased disease and death. Hemostatic agents are used to treat excessive bleeding. A good hemostatic agent controls bleeding effectively, reduces the need for blood transfusion, removes the need for systemic drugs to control bleeding, results in shorter surgery time, and reduces the cost and length of hospital stay of the patient. Gelatin-based hemostatic agents have been widely used in medical and dental procedures, owing to their biodegradability and biocompatibility, as well as availability and low cost of raw materials. In this narrative literature review, we discuss the background and different types of gelatin-based hemostatic agents in medical and dental procedures, the comparison of gelatin-based and non-gelatin-based hemostatic agents, and the usage and development of enhanced or novel gelatin-based hemostatic agents. Gelatin-based hemostatic agents are effective and important part of bleeding control, as evidenced by its wide application in medicine and dentistry. The development of novel combination gelatin-based hemostatic agents has much potential for effective control of excessive bleeding.

Poly(caprolactone)-b-poly(ethylene glycol)-Based Polymeric Micelles as Drug Carriers for Efficient Breast Cancer Therapy: A Systematic Review.

Recently, drug delivery systems based on nanoparticles for cancer treatment have become the centre of attention for researchers to design and fabricate drug carriers for anti-cancer drugs due to the lack of tumour-targeting activity in conventional pharmaceuticals. Poly(caprolactone)-b-poly(ethylene glycol) (PCL-PEG)-based micelles have attracted significant attention as a potential drug carrier intended for human use. Since their first discovery, the Food and Drug Administration (FDA)-approved polymers have been studied extensively for various biomedical applications, specifically cancer therapy. The application of PCL-PEG micelles in different cancer therapies has been recorded in countless research studies for their efficacy as drug cargos. However, systematic studies on the effectiveness of PCL-PEG micelles of specific cancers for pharmaceutical applications are still lacking. As breast cancer is reported as the most prevalent cancer worldwide, we aim to systematically review all available literature that has published research findings on the PCL-PEG-based micelles as drug cargo for therapy. We further discussed the preparation method and the anti-tumour efficacy of the micelles. Using a prearranged search string, Scopus and Science Direct were selected as the databases for the systematic searching strategy. Only eight of the 314 articles met the inclusion requirements and were used for data synthesis. From the review, all studies reported the efficiency of PCL-PEG-based micelles, which act as drug cargo for breast cancer therapy.

Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) Spectroscopy Coupled with Principal Component Analysis and Polymerase Chain Reaction (PCR) Assay for the Detection of Porcine and Bovine Gelatins in Dental Materials.

Muslims are prohibited from consuming products that contain pig products and their derivatives, including porcine gelatin. Medical and dental products are not exempt from the use of gelatin in their formulation. This study employs attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) coupled with principal component analysis (PCA) to detect and distinguish between porcine and bovine gelatins in dental materials. The results were further verified by polymerase chain reaction (PCR) assay. Species-specific primers targeting the 212 bp porcine cytochrome b and 271 bp bovine cytochrome b genes were used to amplify DNA in nine dental material samples. Detection and distinction of gelatin standards (bovine and porcine) against gelatin present in the dental materials was achieved using ATR-FTIR combined with PCA within wavenumber 1756 cm-1-1584 cm-1 (Amide I and Amide II). The detection limit for DNA was 0.001 ng/µL and 0.0001 ng/µL for bovine and porcine gelatins, respectively. Using PCR, one sample, BDM 01, was found to contain both porcine and bovine DNA, while one sample (BDM 14) was found to be positive for bovine DNA. The findings suggest that ATR-FTIR combined with PCA and conventional PCR are applicable for the identification of porcine and bovine gelatin in dental materials.

Natural Products-Based Metallic Nanoparticles as Antimicrobial Agents.

Natural products offer a wide range of bioactivity including antimicrobial properties. There are many reports showing the antimicrobial activities of phytochem icals from plants. However, the bioactivity is limited due to multidrug resistant properties of the microorganism and different composition of cell membrane. The antibacterial activity of the natural products is different toward Gram-negative and Gram-positive bacteria. These phenomena are caused by improper physicochemical conditions of the substance which hinder the phytochemical bioactivity against the broad range of bacteria. One of the strategies to improve the antimicrobial action is by biogenic synthesis via redox balance of the antimicrobial active substance with metal to form nanosized materials or nanoparticles (NPs). Antibiotic resistance is not relevant to NPs because the action of NPs is via direct contact with bacterial cell walls without the need of penetration into microbial cells. The NPs that have shown their effectiveness in preventing or overcoming biofilm formation such as silver-based nanoparticles (AgNPs), gold-based nanoparticles (AuNPs), platinum-based nanoparticles (PtNPs) and Zinc oxide-based nanoparticles (ZnONPs). Due to its considerably simple synthesis procedure has encouraged researchers to explore antimicrobial potency of metallic nanoparticles. Those metallic nanoparticles remarkably express synergistic effects against the microorganisms tested by affecting bacterial redox balance, thus disrupting their homeostasis. In this paper, we discuss the type of metallic nanoparticle which have been used to improve the antimicrobial activity of plant extract/constituents, preparation or synthesis process and characterisation of the plant-based metallic nanoparticles.

A glimpse on the function of chitosan as a dental hemostatic agent.

Managing a bleeding patient can be a challenge during dental surgery. Profuse hemorrhage due to platelet defects, coagulation disorders, vascular anomalies, medication-induced patients, as well as inherited bleeding ailments result in soft tissue hematoma, septic shock, compromised airway, and in some severe cases, death could occur. A vast array of surgical hemostatic agents are available to stop bleeding, including chitosan-based hemostatic agents. Chitosan has an advantage over other topical hemostatic materials for its ability to promote shorter bleeding times and assist in healing. Massive behind-the-scene research and development efforts are ongoing to increase the performance of chitosan as a hemostatic agent. Numerous studies on chitosan use in dental hemostasis have registered it as being safe, biodegradable, biocompatible, promoting healing, antimicrobial and bioactive. This article reviews the application of chitosan in managing hemostasis in dental patients.