MDSC-targeted liposomal all-trans retinoic acid suppresses mMdscs and improves immunotherapy in HBV infection.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are evolving as a prominent determinant in cancer occurrence and development and are functionally found to suppress T cells in cancer. Not much research is done regarding its involvement in viral infections. This research was designed to investigate the role of MDSCs in hepatitis B virus (HBV) infection and how targeting these cells with our novel all-trans retinoic acid encapsulated liposomal formulation could improve immunotherapy in C57BL/6 mice. METHODS: Ten micrograms (10 µg) of plasmid adeno-associated virus (pAAV/HBV 1.2, genotype A) was injected hydrodynamically via the tail vein of C57BL/6 mice. An all-trans retinoic acid encapsulated liposomal formulation (L-ATRA) with sustained release properties was used in combination with tenofovir disoproxil fumarate (TDF), a nucleotide analog reverse transcriptase inhibitor (nRTI) to treat the HBV infection. The L-ATRA formulation was given at a dose of 5 mg/kg intravenously (IV) twice a week. The TDF was given orally at 30 mg/kg daily. RESULTS: Our results revealed that L-ATRA suppresses MDSCs in HBV infected mice and enhanced T-cell proliferation in vitro. In vivo studies showed higher and improved immunotherapeutic effect in mice that received L-ATRA and TDF concurrently in comparison with the groups that received monotherapy. Lower HBV DNA copies, lower concentrations of HBsAg and HBeAg, lower levels of ALT and AST and less liver damage were seen in the mice that received the combination therapy of L-ATRA + TDF. CONCLUSIONS: In effect, targeting MDSCs with the combination of L-ATRA and TDF effectively reduced mMDSC and improved immunotherapy in the HBV infected mice. Targeting MDSCs could provide a breakthrough in the fight against hepatitis B virus infection.

Synthetic berberine derivatives as potential new drugs

Abstract The modern process of new drug discovery and development is an exciting, yet a challenging, endeavor. Although it can result in significant financial income and meet the medical needs of patients, it ultimately may result in failure. To achieve a fast and successful new product discovery and development process, natural products which are evolutionarily optimized as drug-like molecules have gained great attention as better potential sources of new chemical entities. Historically, plant species containing berberine are used in various traditional phytotherapy. However, despite the various therapeutic effects it exerts, berberine is not yet developed into a drug product. Addressing the barriers that hinder its successful development and the efforts made to overcome them is thus crucial. The toxicological and pharmacokinetic properties of berberine are the main barriers towards its development into a marketed drug product. It has low aqueous solubility, poor absorption, fast metabolism, and wide tissue distribution which lead to low bioavailability limiting its clinical application. Synthetic berberine derivatives with improved properties are suggested as better alternatives for further development and future therapeutic application. Hence, this paper summarizes the preclinical research studies conducted in the last decade to reveal the therapeutic potential of synthetic berberine derivatives for the treatment of various diseases and hence achieve successful berberine-based drug development in the future. To exploit the value of natural products as a source of leads for the development of effective drugs, collaboration among the different discovery and development scientists is essential.

Food Protein-Based Nanodelivery Systems for Hydrophobic and Poorly Soluble Compounds.

The hydrophobicity of bioactive molecules poses a considerable problem in the pharmaceutical and the food industry. Using food-based protein nanocarriers is one promising way to deliver hydrophobic molecules. These types of protein possess many functional properties such as surface activity, water-binding capacity, emulsification, foaming, gelation, and antioxidant activity, as well as their incorporation in the food industry as ingredients. Besides, they express low toxicity, are less expensive compared to synthetic polymers, and are biodegradable. This review aims to give a brief overview of the recent studies done using food proteins as colloidal delivery systems for hydrophobic and poorly soluble compounds.

Promising Approach in the Treatment of Glaucoma Using Nanotechnology and Nanomedicine-Based Systems.

Glaucoma is considered a leading cause of blindness with the human eye being one of the body's most delicate organs. Ocular diseases encompass diverse diseases affecting the anterior and posterior ocular sections, respectively. The human eye's peculiar and exclusive anatomy and physiology continue to pose a significant obstacle to researchers and pharmacologists in the provision of efficient drug delivery. Though several traditional invasive and noninvasive eye therapies exist, including implants, eye drops, and injections, there are still significant complications that arise which may either be their low bioavailability or the grave ocular adverse effects experienced thereafter. On the other hand, new nanoscience technology and nanotechnology serve as a novel approach in ocular disease treatment. In order to interact specifically with ocular tissues and overcome ocular challenges, numerous active molecules have been modified to react with nanocarriers. In the general population of glaucoma patients, disease growth and advancement cannot be contained by decreasing intraocular pressure (IOP), hence a spiking in future research for novel drug delivery systems and target therapeutics. This review focuses on nanotechnology and its therapeutic and diagnostic prospects in ophthalmology, specifically glaucoma. Nanotechnology and nanomedicine history, the human eye anatomy, research frontiers in nanomedicine and nanotechnology, its imaging modal quality, diagnostic and surgical approach, and its possible application in glaucoma will all be further explored below. Particular focus will be on the efficiency and safety of this new therapy and its advances.

Targeted and stimuli-responsive mesoporous silica nanoparticles for drug delivery and theranostic use.

For cancer therapy, the usefulness of mesoporous silica nanoparticles (MPSNPs) has been widely discussed, likely due to its inorganic nature and excellent structural features. The MPSNPs-based chemotherapeutics have been promisingly delivered to their target sites that help to minimize side effects and improve therapeutic effectiveness. A wide array of studies have been conducted to functionalize drug-loaded MPSNPs using targeting ligands and stimuli-sensitive substances. In addition, anticancer drugs have been precisely delivered to their target sites using MPSNPs, which respond to multi-stimuli. Furthermore, MPSNPs have been extensively tested for their safety and compatibility. The toxicity level of MPSNPs is substantially lower as compared to that of colloidal silica; however, in oxidative stress, they exhibit cytotoxic features. The biocompatibility of MPSNPs can be improved by modifying their surfaces. This article describes the production procedures, functionalization, and applications of biocompatible MPSNPs in drug delivery.

Recent progress in nanotechnology-based novel drug delivery systems in designing of cisplatin for cancer therapy: an overview.

Cisplatin cis-(diammine)dichloridoplatinum(II) (CDDP) is the first platinum-based complex approved by the food and drug administration (FDA) of the United States (US). Cisplatin is the first line chemotherapeutic agent used alone or combined with radiations or other anti-cancer agents for a broad range of cancers such as lung, head and neck. Aroplatin™, Lipoplatin™ and SPI-077 are PEGylated liposome-based nano-formulations that are still under clinical trials. They have many limitations, for example, poor aqueous solubility, drug resistance and toxicities, which can be overcome by encapsulating the cisplatin in Nemours nanocarriers. The extensive literature from different electronic databases covers the different nano-delivery systems that are developed for cisplatin. This review critically emphasizes on the recent advancement, development, innovations and updated literature reported for different carrier systems for CDDP.

Carbon dots: Applications in bioimaging and theranostics.

Carbon dots are a carbonaceous nanomaterial that were discovered accidentally and are now drawing significant attention as a new quantum-sized fluorescent nanoparticle. Carbon dots are biocompatible, non-toxic, photostable, and easily functionalized with good photoluminescence and water solubility. Due to these unique properties, they are used broadly in live cell imaging, catalysis, electronics, biosensing, power, targeted drug delivery, and other biomedical applications. Here, we review the recent development of carbon dots in nanomedicine from their use in drug carriers to imaging agents to multifunctional theranostic systems. Finally, we discuss the challenges and views on next-generation carbon dot-based theranostics for clinical applications.

Mesoporous Silica Nanomaterials: Versatile Nanocarriers for Cancer Theranostics and Drug and Gene Delivery.

Mesoporous silica nanomaterials (MSNs) have made remarkable achievements and are being thought of by researchers as materials that can be used to effect great change in cancer therapies, gene delivery, and drug delivery because of their optically transparent properties, flexible size, functional surface, low toxicity profile, and very good drug loading competence. Mesoporous silica nanoparticles (MSNPs) show a very high loading capacity for therapeutic agents. It is well known that cancer is one of the most severe known medical conditions, characterized by cells that grow and spread rapidly. Thus, curtailing cancer is one of the greatest current challenges for scientists. Nanotechnology is an evolving field of study, encompassing medicine, engineering, and science, and it has evolved over the years with respect to cancer therapy. This review outlines the applications of mesoporous nanomaterials in the field of cancer theranostics, as well as drug and gene delivery. MSNs employed as therapeutic agents, as well as their importance and future prospects in the ensuing generation of cancer theranostics and drug and therapeutic gene delivery, are discussed herein. Thus, the use of mesoporous silica nanomaterials can be seen as using one stone to kill three birds.

Low-Molecular-Weight Heparins: Reduced Size Particulate Systems for Improved Therapeutic Outcomes.

A wide range of diseases have been treated using low-molecular-weight heparins (LMWHs), the drug of choice for anticoagulation. Owing to their better pharmacokinetic features compared to those of unfractionated heparin (uFH), several systems incorporating LMWHs have been investigated to deliver and improve their therapeutic outcomes, especially through development of their micro- and nano-particles. This review article describes current perspectives on the fabrication, characterization, and application of LMWHs-loaded micro- and nano-particles to achieve ameliorated bioavailability. The valuable applications of LMWH will continue to encourage researchers to identify efficient delivery systems that have specific release characteristics and ameliorated bioavailability, overcoming the challenges presented by biological obstructions and the physicochemical properties of LMWHs.

A pilot study evaluating the prescribing of ceftriaxone in hospitals in Ghana: findings and implications.

BACKGROUND AND OBJECTIVES: Widespread empiric use of antibiotics exists especially in developing countries. This is a concern since inappropriate use of antibiotics, including their extended inappropriate use, will increase resistance rates. Consequently, there is a need to evaluate antibiotic utilisation across healthcare sectors to improve future use. This includes ceftriaxone, widely used among hospitals including those in Ghana. METHODS: A cross-sectional study to evaluate the appropriateness of ceftriaxone prescribing in a leading hospital in Ghana. Ceftriaxone prescribing in patient-record cards was assessed using a modified WHO drug-utilization evaluation criteria as well as referencing the national standard treatment guidelines in Ghana and the ceftriaxone package insert. RESULTS: A total of 251 patients were assessed. Ceftriaxone was most commonly prescribed for comorbid malaria with bacterial infections, urinary tract infections, sepsis and gastroenteritis. The appropriateness of the indication was 86% (n = 218). The doses most prescribed were 1g (41%) and 2g (39%). Stat dose and once-daily dosage regimen constituted 51.4% and 84.5%, respectively. The most common duration of treatment was 1 (51.4%) and 2 days (35.1%). The overall appropriateness of prescribing was 93% against a pre-set threshold of 97%. CONCLUSION: The appropriateness of ceftriaxone prescribing was high in this leading hospital in Ghana; however, there is room for improvement with targeted education initiatives, with further research planned.