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Physiologically-based biopharmaceutics modeling (PBBM) has potential to accelerate the development of new drug and formulations. An important application of PBBM is for special populations such as pediatrics that have pharmacokinetics dependent on the maturation process. Lamotrigine (LTG) is a Biopharmaceutics Classification System (BCS) II drug and is widely prescribed. Therefore, the goal of this study was to assess the biopharmaceutics risk of the low-soluble drug LTG when the ontogeny on gastrointestinal tract (GIT) physiological parameters are considered. An oral physiologically-based pharmacokinetic model and a PBBM were developed and verified using GastroPlus™ software for both adults and children (2-12 years old, 12-52 kg). The biopharmaceutics properties and GIT physiological parameters were evaluated by sensitivity analysis. High doses were simulated assuming a worst case scenario, that is, the dose of 200 mg for adults and 5 mg/kg (up to the maximum of 200 mg) for 2-year-old children. Although several authors have suggested that ontogeny may have an effect on gastrointestinal fluid volume, our study found no evidence of interference between fluid and dose volumes with in vivo dissolution of LTG. The most impactful parameter was found to be the gastric transit time. Therefore, the hypothesis is developed to examine whether LTG exhibits characteristics of a BCS II classification in vitro while showing BCS I-like behavior in vivo. This hypothesis could act as a base for conducting novel studies on model-informed precision dosing, tailored to specific populations and clinical conditions. In addition, it could be instrumental in assessing the influence of various release profiles on in vivo performance for both adult and pediatric populations., (© 2023 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

The primary cause of atherosclerotic cardiovascular disease (ASCVD) is elevated levels of low-density lipoprotein cholesterol (LDL-C). Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in this process by binding to the LDL receptor (LDL-R) domain, leading to reduced influx of LDL-C and decreased LDL-R cell surface presentation on hepatocytes, resulting higher circulating levels of LDL-C. As a consequence, PCSK9 has been identified as a crucial target for drug development against dyslipidemia and hypercholesterolemia, aiming to lower plasma LDL-C levels. This research endeavors to identify promising inhibitory candidates that target the allosteric site of PCSK9 through an in silico approach. To start with, the FDA-approved Drug Library from Selleckchem was selected and virtually screened by docking studies using Glide extra-precision (XP) docking mode and Smina software (Version 1.1.2). Subsequently, rescoring of 100 drug compounds showing good average docking scores were performed using Gnina software (Version 1.0) to generate CNN Score and CNN binding affinity. Among the drug compounds, amikacin, bestatin, and natamycin were found to exhibit higher docking scores and CNN affinities against the PCSK9 enzyme. Molecular dynamics simulations further confirmed that these drug molecules established the stable protein-ligand complexes when compared to the apo structure of PCSK9 and the complex with the co-crystallized ligand structure. Moreover, the MM-GBSA calculations revealed binding free energy values ranging from -84.22 to -76.39 kcal/mol, which were found comparable to those obtained for the co-crystallized ligand structure. In conclusion, these identified drug molecules have the potential to serve as inhibitors PCSK9 enzyme and these finding could pave the way for the development of new PCSK9 inhibitory drugs in future in vitro research.

We present an enhanced method for synthesizing a novel compound, 1-(4-phenylquinolin-2-yl)propan-1-one ( 3 ), through the solvent-free Friedländer quinoline synthesis using poly(phosphoric acid) as an assisting agent. The crystal structure of compound 3 is analyzed using FT-IR, and the chemical shifts of its 1 H- and 13 C NMR spectra are measured and calculated using B3LYP/6-311G(d,p), CAM-B3LYP/6-311G(d,p), and M06-2X/6-311G(d,p) basis sets in the gas phase. Additionally, the optimized geometry of quinoline 3 is compared with experimental X-ray diffraction values. Through density functional theory calculations, we explore various aspects of the compound's properties, including noncovalent interactions, Hirshfeld surface analysis, nonlinear optical properties, thermodynamic properties, molecular electrostatic potential, and frontier molecular orbitals. These investigations reveal chemically active sites within this quinoline derivative that contribute to its chemical reactivity., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

This review explores the potential of photonic nanoparticles for cancer theranostics. Photonic nanoparticles offer unique properties and photonics capabilities that make them promising materials for cancer treatment, particularly in the presence of near-infrared light. However, the size of the particles is crucial to their absorption of near-infrared light and therapeutic potential. The limitations and challenges associated with the clinical use of photonic nanoparticles, such as toxicity, immune system clearance, and targeted delivery to the tumor are also discussed. Researchers are investigating strategies such as surface modification, biodegradable nanoparticles, and targeting strategies to improve biocompatibility and accumulation in the tumor. Ongoing research suggests that photonic nanoparticles have potential for cancer theranostics, further investigation and development are necessary for clinical use.

Nanotechnology is an arena of exploration and innovation concerned with building things generally, advancing resources and devices based on highly specific and superior nanomaterials with unmatched properties dependent on their morphology and diameter. 2D materials such as graphene have unique properties and applications varying from imaging, delivery of drugs, and theranostics of diseases. Each 2D material, ranging from the graphene family, MXenes, chalcogenides, and 2D oxides, have a unique potential based on their shape and morphology. In addition, 2D materials have intriguing physiochemical characteristics, increased aspect ratio and associated increased reactivity that make them an ideal contender in multiple applications. This review aims to answer the existing knowledge gaps in various 2D materials having interdisciplinary roles. We have presented a brief overview of the 2D materials, followed by their synthesis methods and techniques. We have also highlighted the different characterization methods used to characterise various 2D materials. Next, we performed an in-depth analysis of the potential toxicities of 2D materials to assess their risks in multiple applications. Lastly, we conclude our review by presenting the challenges and future perspectives of 2D materials as promising forerunners of science and technology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Ligand-based targeting of the receptors that are overexpressed explicitly on cancer cells represents an effective drug delivery approach to enhance the chemotherapeutic efficacy. Proprotein convertase subtilisin/kexin type 9 (PCSK9) which is a serine protease enzyme primarily produced by the liver cells, can potentially be used as a targeting ligand. PCSK9 binds to the LDL-r on hepatocytes' surface, leading to endocytosis and endosomal degradation. High LDL-r expression, which is believed to meet the higher demand of the cholesterol and phospholipids to build proliferating cancer cell membrane, ensures selective uptake of the PCSK9 conjugated liposomes. In the present work, the PCSK9 conjugated liposomal system was developed to deliver paclitaxel (PTX) to cancer cells. The protein was conjugated by EDC and NHS in a two-step coupling reaction to the liposomes containing COOH-PEG 2000 -COOH lipid. Conjugation was confirmed by NMR, and liposomes were further characterized by SEM and zeta sizer. PCSK9-conjugated liposomes showed high encapsulation efficiency of 69.1% with a diameter of 90.0 ± 4.9 nm. Long-term stability (30 days) study (Zeta potential: -9.88) confirmed excellent constancy and significant drug retention (58.2%). Invitro cytotoxicity and targeting efficiency was explored using MTS assay in human embryonic kidney cells (HEK293), liver hepatocellular cells (HEPG2), and a human colon cancer cell line (HCT116) for 24 h. PCSK9 conjugated liposomes exhibited significantly higher growth inhibition than the unconjugated (control) liposomes in HCT116 cell line (p < 0.001). The novel PCSK9 conjugated liposomes presented potent and precise in vitro anticancer activity and, therefore, are suggested for the first time as a promising targeted delivery system for cancer treatment., Competing Interests: Conflict of interest statement All Authors declare No Conflict of Interest., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Anatomical complications of the craniofacial regions often present considerable challenges to the surgical repair or replacement of the damaged tissues. Surgical repair has its own set of limitations, including scarcity of the donor tissues, immune rejection, use of immune suppressors followed by the surgery, and restriction in restoring the natural aesthetic appeal. Rapid advancement in the field of biomaterials, cell biology, and engineering has helped scientists to create cellularized skeletal muscle-like structures. However, the existing method still has limitations in building large, highly vascular tissue with clinical application. With the advance in the three-dimensional (3D) bioprinting technique, scientists and clinicians now can produce the functional implants of skeletal muscles and bones that are more patient-specific with the perfect match to the architecture of their craniofacial defects. Craniofacial tissue regeneration using 3D bioprinting can manage and eliminate the restrictions of the surgical transplant from the donor site. The concept of creating the new functional tissue, exactly mimicking the anatomical and physiological function of the damaged tissue, looks highly attractive. This is crucial to reduce the donor site morbidity and retain the esthetics. 3D bioprinting can integrate all three essential components of tissue engineering, that is, rehabilitation, reconstruction, and regeneration of the lost craniofacial tissues. Such integration essentially helps to develop the patient-specific treatment plans and damage site-driven creation of the functional implants for the craniofacial defects. This article is the bird's eye view on the latest development and application of 3D bioprinting in the regeneration of the skeletal muscle tissues and their application in restoring the functional abilities of the damaged craniofacial tissue. We also discussed current challenges in craniofacial bone vascularization and gave our view on the future direction, including establishing the interactions between tissue-engineered skeletal muscle and the peripheral nervous system., (© 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

The efficacy of chemotherapy depends on the tumor microenvironment. This microenvironment consists of a complex cellular network that can exert both stimulatory and inhibitory effects on tumor genesis. Given the increasing interest in the effectiveness of cannabis, cannabinoids have gained much attention as a potential chemotherapy drug. Cannabinoids are a group of marker compounds found in Cannabis sativa L., more commonly known as marijuana, a psychoactive drug used since ancient times for pain management. Although the anticancer potential of C. sativa , has been recognized previously, increased attention was generated after discovering the endocannabinoid system and the successful production of cannabinoid receptors. In vitro and in vivo studies on various tumor models have shown therapeutic efficiency by modifying the tumor microenvironment. However, despite extensive attention regarding potential therapeutic implications of cannabinoids, considerable clinical and preclinical analysis is needed to adequately define the physiological, pharmacological, and medicinal aspects of this range of compounds in various disorders covered in this review. This review summarizes the key literature surrounding the role of cannabinoids in the tumor microenvironment and their future promise in cancer treatment.

More than five decades have been invested in understanding glucose biosensors. Yet, this immensely versatile field has continued to gain attention from the scientific world to better understand and diagnose diabetes. However, such extensive work done to improve glucose sensing devices has still not yielded desirable results. Drawbacks like the necessity of the invasive finger-pricking step and the lack of optimization of diagnostic interventions still need to be considered to improve the testing process of diabetic patients. To upgrade the glucose-sensing devices and reduce the number of intermediary steps during glucose measurement, fourth-generation glucose sensors (FGGS) have been introduced. These sensors, made using robust electrocatalytic copper nanostructures, improve diagnostic efficiency and cost-effectiveness. This review aims to present the essential scientific progress in copper nanostructure-based FGGS in the past 10 years (2010 to present). After a short introduction, we presented the working principles of these sensors. We then highlighted the importance of copper nanostructures as advanced electrode materials to develop reliable real-time FGGS. Finally, we cover the advantages, shortcomings, and prospects for developing highly sensitive, stable, and specific FGGS., Competing Interests: The authors declare no potential conflict of interest., (© 2021 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

The purpose of this review is to highlight recent scientific developments and provide an overview of virus self-assembly and viral particle dynamics. Viruses are organized supramolecular structures with distinct yet related features and functions. Plant viruses are extensively used in biotechnology, and virus-like particulate matter is generated by genetic modification. Both provide a material-based means for selective distribution and delivery of drug molecules. Through surface engineering of their capsids, virus-derived nanomaterials facilitate various potential applications for selective drug delivery. Viruses have significant implications in chemotherapy, gene transfer, vaccine production, immunotherapy and molecular imaging., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript., (© 2021 The authors.)

In many ways, cancer cells are different from healthy cells. A lot of tactical nano-based drug delivery systems are based on the difference between cancer and healthy cells. Currently, nanotechnology-based delivery systems are the most promising tool to deliver DNA-based products to cancer cells. This review aims to highlight the latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer cells. It also provides the necessary information about siRNA development and its mechanism of action. Overall, this review gives us a clear picture of lipid and polymer-based drug delivery systems, which in the future could form the base to translate the basic siRNA biology into siRNA-based cancer therapies., Competing Interests: The authors have no conflicts of interest to declare., (© 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Piceatannol (PIC) is known to have anticancer activity, which has been attributed to its ability to block the proliferation of cancer cells via suppression of the NF-kB signaling pathway. However, its effect on hypoxia-inducible factor (HIF) is not well known in cancer. In this study, PIC was loaded into bovine serum albumin (BSA) by desolvation method as PIC-BSA nanoparticles (NPs). These PIC-BSA nanoparticles were assessed for in vitro cytotoxicity, migration, invasion, and colony formation studies and levels of p65 and HIF-1α. Our results indicate that PIC-BSA NPs were more effective in downregulating the expression of nuclear p65 and HIF-1α in colon cancer cells as compared to free PIC. We also observed a significant reduction in inflammation induced by chemical colitis in mice by PIC-BSA NPs. Furthermore, a significant reduction in tumor size and number of colon tumors was also observed in the murine model of colitis-associated colorectal cancer, when treated with PIC-BSA NPs as compared to free PIC. The overall results indicate that PIC, when formulated as PIC-BSA NPs, enhances its therpautice potential. Our work could prompt further research in using natural anticancer agents as nanoparticels with possiable human clinical trails. This could lead to the development of a new line of safe and effective therapeutics for cancer patients., Competing Interests: The authors declare no conflicts of interest.

Three-dimensional (3D) printing, also known as additive manufacturing, was developed originally for engineering applications. Since its early advancements, there has been a relentless development in enthusiasm for this innovation in biomedical research. It allows for the fabrication of structures with both complex geometries and heterogeneous material properties. Tissue engineering using 3D bio-printers can overcome the limitations of traditional tissue engineering methods. It can match the complexity and cellular microenvironment of human organs and tissues, which drives much of the interest in this technique. However, most of the preliminary evaluations of 3Dprinted tissues and organ engineering, including cardiac tissue, relies extensively on the lessons learned from traditional tissue engineering. In many early examples, the final printed structures were found to be no better than tissues developed using traditional tissue engineering methods. This highlights the fact that 3D bio-printing of human tissue is still very much in its infancy and more work needs to be done to realise its full potential. This can be achieved through interdisciplinary collaboration between engineers, biomaterial scientists and molecular cell biologists. This review highlights current advancements and future prospects for 3D bio-printing in engineering ex vivo cardiac tissue and associated vasculature, such as coronary arteries. In this context, the role of biomaterials for hydrogel matrices and choice of cells are discussed. 3D bio-printing has the potential to advance current research significantly and support the development of novel therapeutics which can improve the therapeutic outcomes of patients suffering fatal cardiovascular pathologies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Orally administered solid dosage forms currently dominate over all other dosage forms and routes of administrations. However, human gastrointestinal tract (GIT) poses a number of obstacles to delivery of the drugs to the site of interest and absorption in the GIT. Pharmaceutical scientists worldwide have been interested in colon drug delivery for several decades, not only for the delivery of the drugs for the treatment of colonic diseases such as ulcerative colitis and colon cancer but also for delivery of therapeutic proteins and peptides for systemic absorption. Despite extensive research in the area of colon targeted drug delivery, we have not been able to come up with an effective way of delivering drugs to the colon. The current tablets designed for colon drug release depend on either pH-dependent or time-delayed release formulations. During ulcerative colitis the gastric transit time and colon pH-levels is constantly changing depending on whether the patient is having a relapse or under remission. Hence, the current drug delivery system to the colon is based on one-size-fits-all. Fails to effectively deliver the drugs locally to the colon for colonic diseases and delivery of therapeutic proteins and peptides for systemic absorption from the colon. Hence, to overcome the current issues associated with colon drug delivery, we need to provide the patients with personalized tablets which are specifically designed to match the individual's gastric transit time depending on the disease state. Three-dimensional (3D) printing (3DP) technology is getting cheaper by the day and bespoke manufacturing of 3D-printed tablets could provide the solutions in the form of personalized colon drug delivery system. This review provides a bird's eye view of applications and current advances in pharmaceutical 3DP with emphasis on the development of colon targeted drug delivery systems., Competing Interests: There are no conflicts of interest.