Getting Proactive with Pharma Packaging

According to market research, the pharmaceutical packaging sector is expected to grow at a compound annual rate of 7.4% between 2022 and 2031, reaching an estimated USS178.8 billion (€171.8 billion) by the end of the forecast period (1). "Pharmaceutical waste continues to be a huge problem, so to eliminate non-biodegradable and single-use plastics from the supply chain, more research is taking place around bio-based PET [polyethylene terephthalate]. "By designing a product's primary and secondary packaging well from the outset (including investing ample resources into the process), manufacturers can reduce the amount of materials used and wasted, test new eco materials, ensure safety compliance and efficacy, and benefit from cheaper transportation costs," Quelch surmises. [...]pharma companies can benefit from a packaging supplier with a true global footprint," he says.

Connecting the Dots for Pharma

A major driver for innovation within the bio/pharma sector has been the COVID-19 pandemic, which propelled advances such as the approval of messenger RNA (mRNA) vaccines at record-breaking speeds and led to many companies pivoting to deal with the urgent requirements for capacity and supply chain flexibility needed to overcome pandemic challenges. "Before deciding on a location, we conducted extensive market research, and it quickly became clear, just by the sheer proximity of so many biopharmaceutical companies, associations, and research centres, that the event had to be in Geneva. Organized as four half-days, they will each address a theme related to the four main areas of the supply chain present in the exhibition area: pharmaceutical packaging (primary and secondary), medical devices, pharmaceutical sub-contracting, and pharmaceutical equipment. The dream scenario, the real measure of success, is when a product comes to market that happened as a result of a meeting or discussion that took place at our event.

Cracking the Code of Complex Drug Modalities via Multidimensional Liquid Chromatography Coupled to Mass Spectrometry

Reducing the molecule complexity is achieved by reducing the molecule size after enzymatic digestion to produce smaller fragments more amenable to LC separation and tandem mass spectrometry (MS/MS) sequencing. Non-denaturing CEX chromatography, size-exclusion chromatogra- phy (SEC), hydrophobic interaction chromatography (HIC), and protein A modes can be easily coupled to reversed-phase LC (RPLC) because of the high aqueous conditions, enabling the versatile 4D-LC-MS systems with the use of alternative modes to 1D CEX, such as SEC or Protein A (6,7). [...]the nanopar-ticle size and free drug concentration are determined at the particle Level, whereas the encapsulated drug and lipids forming the layer are commonly characterized at the molecuar level after denaturing the lipid nanoparticle (LNP) via a surfactant. [...]MDLC-MS setups present a formidable opportunity to unify the characterization of drug delivery systems at the molecular and particle evels, which would enable their high throughput analysis.

Compelling Impacts of Natural Polymer-Centered Drug Delivery Systems as Prophylactic and Therapeutic Approaches in Various Pulmonary Disorders/Lung Diseases

Pulmonary disorders are common illness that affects people of all ages world­wide. Common pulmonary disorders include pulmonary hypertension, CF (cystic fibrosis), asthma, chronic obstructive pulmonary disorder, emphysema, chronic bronchitis, lung cancer, and COVID-19. Treatments of these disorders vary but can be broadly categorized into pharmacological (medicinal), non-pharmacological, rehabilitation, and surgical techniques. Often, a combina­tion of these approaches is used, both for symptomatic relief and treatment. Regarding these prophylactic and therapeutic approaches, advances are rapidly being made, and scientists are currently investigating modern and unique theranostic methods. However, there is a lacuna in drug delivery, pharmacokinetic aspects, and drug-induced adverse effects. One particular area for improvement that needs to be immediately addressed is the drug delivery system to significantly improve healthcare associated with pulmonary disorders. Natural polymer-based drug delivery systems are widely adopted for their ease of production, lack of biotoxicity, and strong bioaffinity. Of the natural polymer­based drug delivery systems, chitosan, sodium alginates, albumin, hydroxyapa­tite, and hyaluronic acid are the most common natural polymers. Each of these natural polymers has its preferred use, either due to tissue-specific delivery or medical property packaging. The current scientific article discusses the common pulmonary disorders, their pathophysiology, and the current therapeutic approaches. Additionally, we discuss the major natural polymer drug delivery systems, including their properties and common uses. © The Author (s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.

Development of therapeutic antibodies for the treatment of infection diseases and future aspect

Since the late 1990s, therapeutic antibodies have been developed for various oncology and immunoinflammatory diseases. To date, more than 100 therapeutic antibodies have been approved in Japan, the U.S., and Europe for these indications. In contrast, the development of antibody drugs in the field of infectious diseases has been limited so far. The recent SARS-CoV-2 pandemic has highlighted the importance of therapeutic antibodies for infectious diseases as well as the development of drug delivery systems（DDS）. This review summarizes the past development of antibody drugs for infectious diseases and provides a future perspective of how therapeutic antibodies can be developed by utilizing antibody engineering and DDS technologies.Alternate :抄録1990年代後半に、がん領域や免疫炎症性疾患領域において、抗体医薬品が画期的な治療効果を示して以降、さまざまな疾患領域において抗体医薬品の研究開発がなされ、現在までに日米欧で100品目を超える抗体医薬品が承認されている。感染症領域における抗体医薬品の開発は限られていたが、抗体工学の発展、SARS-CoV-2の感染の拡大により、感染症領域における抗体医薬品の重要性が注目されている。本稿では、これまでの感染症領域における抗体医薬品の開発と、抗体工学やDDS技術の進展に伴う今後の抗体医薬品の展望を概説する。

A dispersion-corrected DFT calculation on encapsulation of favipiravir drug used as antiviral against COVID-19 into carbon-, boron-, and aluminum-nitride nanotubes for optimal drug delivery systems combined with molecular docking simulations.

Favipiravir (FAV) (6-fluoro-3-oxo-3,4-dihydropyrazine-2-carboxamide) is one of the most effective antiviral drugs which is cited for action against RNA-viral infections of COVID-19. In this study, density functional theory (DFT) calculations were used to investigate three nanotubes (NTs) with FAV drug as delivery systems. The encapsulated systems (ESs) consist of FAV drug inside carbon-carbon, aluminum nitride, and boron nitride. At B3LYP-D/6-31G(d,p) and CPCM/B3LYP-D/6-31G(d,p), the optimization of NTs, FAV, and its tautomeric forms and six ESs was investigated in gas and water environments. Five tautomeric forms of FAV were investigated, two keto forms (K1 and K2) and three enol forms (E1, E2, and E3). The results revealed that E3 and K2 isomeric forms represented the most stable structures in both media; thus, these two forms were encapsulated into the NTs. The stability and the synthesis feasibility of NTs have been proven by calculating their interaction energies. Non-covalent interactions (NCIs) were investigated in the ESs to show the type of NCI with the molecular voids. The binding energies, thermochemical parameters, and recovery times were investigated to understand the mechanism of FAV encapsulation and release. The encapsulated AlNNT systems are more favorable than those of BNNTs and CNTs in gas and aqueous environments with much higher binding energies. The quantum theory of atoms in molecules (QTAIM) and recovery time analysis revealed the easier releasing of E3 from AlNNT over K2 form. Based on molecular docking simulations, we found that E3 and K2 FAV forms showed a high level of resistance to SARS-CoV-6M3M/6LU7/6W9C proteases. Supplementary Information: The online version contains supplementary material available at 10.1007/s11224-023-02182-4.

Biodegradable Polymer Nanoparticles: Therapeutic Applications and Challenges

The greatest medication encapsulation and distribution options have received substantial research on biodegradable natural polymers. For their potential to act as an effective vehicle for site-specific medication delivery in the body, biodegradable nanoparticles (NPs) are attracting more interest. They provide enhanced biocompatibility, and practical release patterns for a variety of medicines to be used in a number of applications. This article has explored the various applications of these particles, including cancer therapy, implantable device, and antioxidant delivery. However, there is still potential to investigate more biodegradable polymers for cutting-edge biological applications.

Recent Advances in Strategies to Combat Bacterial Drug Resistance: Antimicrobial Materials and Drug Delivery Systems.

Bacterial infection is a common clinical disease. Antibiotics have saved countless lives since their discovery and are a powerful weapon in the fight against bacteria. However, with the widespread use of antibiotics, the problem of drug resistance now poses a great threat to human health. In recent years, studies have investigated approaches to combat bacterial resistance. Several antimicrobial materials and drug delivery systems have emerged as promising strategies. Nano-drug delivery systems for antibiotics can reduce the resistance to antibiotics and extend the lifespan of novel antibiotics, and they allow targeting drug delivery compared to conventional antibiotics. This review highlights the mechanistic insights of using different strategies to combat drug-resistant bacteria and summarizes the recent advancements in antimicrobial materials and drug delivery systems for different carriers. Furthermore, the fundamental properties of combating antimicrobial resistance are discussed, and the current challenges and future perspectives in this field are proposed.

Plant-derived nanovesicles: further exploration of biomedical function and application potential

Extracellular vesicles (EVs) are phospholipid bilayer vesicles actively secreted by cells, that contain a variety of functional nucleic acids, proteins, and lipids, and are important mediums of intercellular communication. Based on their natural properties, EVs can not only retain the pharmacological effects of their source cells but also serve as natural delivery carriers. Among them, plant-derived nanovesicles (PNVs) are characterized as natural disease therapeutics with many advantages such as simplicity, safety, eco-friendliness, low cost, and low toxicity due to their abundant resources, large yield, and low risk of immunogenicity in vivo. This review systematically introduces the biogenesis, isolation methods, physical characterization, and components of PNVs, and describes their administration and cellular uptake as therapeutic agents. We highlight the therapeutic potential of PNVs as therapeutic agents and drug delivery carriers, including anti-inflammatory, anticancer, wound healing, regeneration, and antiaging properties as well as their potential use in the treatment of liver disease and COVID-19. Finally, the toxicity and immunogenicity, the current clinical application, and the possible challenges in the future development of PNVs were analyzed. We expect the functions of PNVs to be further explored to promote clinical translation, thereby facilitating the development of a new framework for the treatment of human diseases.Copyright © 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences

Vitamins and SARS-CoV-2

Vitamins are very important to stay healthy. Taking macronutrients and micronutrients based on the body's needs prevents us from diseases and can treat them. Vitamins have proven to help deal with severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) patients. Vitamin C intake seems to boost immunity. Several studies suggested that vitamin C intake can lower the extent of upper respiratory tract infections (URTIs) besides its other biological functions such as collagen formation and wound healing. Vitamin C works as an anti-oxidant, counteracting the free radicals during an infection. Whenever an infection or disease occurs, it causes the production of reactive oxygen species, or such oxidizing agents help in the inactivation of viruses. Vitamin D is another important micronutrient to treat and prevent URTIs. Commonly, it is recommended for bone and teeth health, but it has also been used for regulating and boosting the immune system. Nutraceutical applications of vitamins are inevitable. Different natural products and foods are good sources of vitamins that can be taken for improved functions of the human body and treatment of diseases. Besides the oral route, vitamins C and D can also be supplied via micro or nanoparticles through other routes. An adequate intake of vitamins positively affects the body in the fight against infections. So, it can also help reduce the severity of illness and morbidity of patients suffering from SARS-CoV-2 infection. © 2023 Elsevier Inc. All rights reserved.

Ionizable drug delivery systems for efficient and selective gene therapy.

Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function. However, a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells. To be excited, the development of ionizable drug delivery systems (IDDSs) has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019 (COVID-19) in 2021. Compared with conventional cationic gene vectors, IDDSs can decrease the toxicity of carriers to cell membranes, and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures. Despite the progress, there remain necessary requirements for designing more efficient IDDSs for precise gene therapy. Herein, we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms. The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of pDNA and four kinds of RNA. In particular, organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity. We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future, and indicate ideas for developing next generation gene vectors.

Oral Bioactive Self-Nanoemulsifying Drug Delivery Systems of Remdesivir and Baricitinib: A Paradigmatic Case of Drug Repositioning for Cancer Management.

Oral anticancer therapy mostly faces the challenges of low aqueous solubility, poor and irregular absorption from the gastrointestinal tract, food-influenced absorption, high first-pass metabolism, non-targeted delivery, and severe systemic and local adverse effects. Interest has been growing in bioactive self-nanoemulsifying drug delivery systems (bio-SNEDDSs) using lipid-based excipients within nanomedicine. This study aimed to develop novel bio-SNEDDS to deliver antiviral remdesivir and baricitinib for the treatment of breast and lung cancers. Pure natural oils used in bio-SNEDDS were analyzed using GC-MS to examine bioactive constituents. The initial evaluation of bio-SNEDDSs were performed based on self-emulsification assessment, particle size analysis, zeta potential, viscosity measurement, and transmission electron microscopy (TEM). The single and combined anticancer effects of remdesivir and baricitinib in different bio-SNEDDS formulations were investigated in MDA-MB-231 (breast cancer) and A549 (lung cancer) cell lines. The results from the GC-MS analysis of bioactive oils BSO and FSO showed pharmacologically active constituents, such as thymoquinone, isoborneol, paeonol and p-cymenene, and squalene, respectively. The representative F5 bio-SNEDDSs showed relatively uniform, nanosized (247 nm) droplet along with acceptable zeta potential values (+29 mV). The viscosity of the F5 bio-SNEDDS was recorded within 0.69 Cp. The TEM suggested uniform spherical droplets upon aqueous dispersions. Drug-free, remdesivir and baricitinib-loaded bio-SNEDDSs (combined) showed superior anticancer effects with IC50 value that ranged from 1.9-4.2 µg/mL (for breast cancer), 2.4-5.8 µg/mL (for lung cancer), and 3.05-5.44 µg/mL (human fibroblasts cell line). In conclusion, the representative F5 bio-SNEDDS could be a promising candidate for improving the anticancer effect of remdesivir and baricitinib along with their existing antiviral performance in combined dosage form.

Recent Progress of Lipid Nanoparticles-Based Lipophilic Drug Delivery: Focus on Surface Modifications.

Numerous drugs have emerged to treat various diseases, such as COVID-19, cancer, and protect human health. Approximately 40% of them are lipophilic and are used for treating diseases through various delivery routes, including skin absorption, oral administration, and injection. However, as lipophilic drugs have a low solubility in the human body, drug delivery systems (DDSs) are being actively developed to increase drug bioavailability. Liposomes, micro-sponges, and polymer-based nanoparticles have been proposed as DDS carriers for lipophilic drugs. However, their instability, cytotoxicity, and lack of targeting ability limit their commercialization. Lipid nanoparticles (LNPs) have fewer side effects, excellent biocompatibility, and high physical stability. LNPs are considered efficient vehicles of lipophilic drugs owing to their lipid-based internal structure. In addition, recent LNP studies suggest that the bioavailability of LNP can be increased through surface modifications, such as PEGylation, chitosan, and surfactant protein coating. Thus, their combinations have an abundant utilization potential in the fields of DDSs for carrying lipophilic drugs. In this review, the functions and efficiencies of various types of LNPs and surface modifications developed to optimize lipophilic drug delivery are discussed.

Inhalation Vaccine Development: Inhaled vaccines must resist degradation and penetrate the mucosal lining in the airways and lungs

The article offers update on inhalation vaccine development. Topics discussed are advantages and challenges of administering inhalation vaccines, powder and liquid formulations of inhalation vaccines, psychochemical attributes of vaccine actives essential for successful inhalation delivery, importance of the development of optimized vaccine/device combination, regulatory hurdles to inhalation vaccine development, and other inhaled COVID-19 vaccines in development such as peptide vaccines.

Effect of Cholesterol Content of Lipid Composition in mRNA-LNPs on the Protein Expression in the Injected Site and Liver After Local Administration in Mice.

Delivery of messenger RNA (mRNA) using lipid nanoparticles (LNPs) is expected to be applied to various diseases following the successful clinical use of the mRNA COVID-19 vaccines. This study aimed to evaluate the effect of the cholesterol molar percentage of mRNA-LNPs on protein expression in hepatocellular carcinoma-derived cells and in the liver after intramuscular or subcutaneous administration of mRNA-LNPs in mice. For mRNA-LNPs with cholesterol molar percentages reduced to 10 mol% and 20 mol%, we formulated neutral charge particles with a diameter of approximately 100 nm and polydispersity index (PDI) <0.25. After the intramuscular or subcutaneous administration of mRNA-LNPs with different cholesterol molar percentages in mice, protein expression in the liver decreased as the cholesterol molar percentage in mRNA-LNPs decreased from 40 mol% to 20 mol% and 10 mol%, suggesting that reducing the cholesterol molar percentage in mRNA-LNPs decreases protein expression in the liver. Furthermore, in HepG2 cells, protein expression decreased as cholesterol in mRNA-LNPs was reduced by 40 mol%, 20 mol%, and 10 mol%. These results suggest that the downregulated expression of mRNA-LNPs with low cholesterol content in the liver involves degradation in systemic circulating blood and decreased protein expression after hepatocyte distribution.

p-Cresol in the Simulated Biological Fluids

[...]this idea proposes that CD-NS details are secure and successful in expelling harmful atoms from the body. Understanding who is habitually dialyzed for the urea clearance is lower by six times when analyzing its strength with a well-being person. [...]urinary toxins aggregate into the body due to inadequate kidney function. The most beneficial system is found to be CD-based. Because CD-based systems for many years have been used as pharmaceutical excipients and are natural biocompatible polymers16,17,18. [...]it produces a rigid structure that shapes the nanoparticles54.

Herbal Medicines as Potential Immune Boosters against Coronavirus Diseases

Coronavirus disease COVID-19 is causing havoc globally, infecting millions of people and has led to the deaths of people in thousands. COVID-19 attacks persons with low immune sys-tems, especially neonates and geriatrics. Hence, boosting immunity may be one of the best options during this pandemic. There is a need to explore the possible herbal drugs to boost the immunity of people as a result of the rising cases of deaths due to COVID-19. However, the rationale for the use of herbal drugs is that each herb has the possibility of treating many health conditions. A single herb could have antiviral, antibacterial, and anti-inflammatory properties. Herbs may be one possible source of a true cure for COVID-19. Herbal drugs are from renewable sources and pose less danger of possible adverse effects compared to synthetic drugs. Because COVID-19 has no true cure pres-ently, man should resort to herbal drugs given by nature. Herbal drugs are highly potent and effica-cious;hence, the early men treated their ailments with herbs. However, their use has been limited by poor pharmaceutical design into dosage forms that would be acceptable to people. Herbal drugs could be formulated as teas, decoctions, infusions, and, more recently, tablets, capsules, microparti-cles, nanoparticles, and phytosomes, amongst others. Different herbal plants with possible immune booster effects will be discussed in this work, and how they can be formulated into stable and acceptable dosage forms will be explored. Copyright © 2023 Bentham Science Publishers.

Engineered self-healing single-cavity microcapsules for pulsatile release of drug delivery

A wide range of polymer-based drug delivery systems have been reported for the treatment of various diseases. However, the dosing regimen of many drugs, such as stimulator of interferon genes agonists, programmed cell death protein-1 antibodies, and coronavirus disease 2019 vaccines, consists of repeated intratumoral or intramuscular injections. These repeated administrations may lead to poor adherence, thus resulting in compromised therapeutic outcomes and increased financial burden. Here, we developed a multidose drug delivery platform by engineering polylactic-co-glycolic acid (PLGA) with different molecular weights into self-healing single-cavity microcapsules (SSM). This approach showed a flexible collocation strategy to achieve customized pulsatile drug release and was fully degradable with good safety. Notably, this single-injection delivery system contains only PLGA, holding great promise for clinical translation. © 2022 Chinese Society of Particuology and Institute of Process Engineering, Chinese Academy of Sciences

Pharmacological Activity, Pharmacokinetics, and Clinical Research Progress of Puerarin.

As a kind of medicine and food homologous plant, kudzu root (Pueraria lobata (Willd.) Ohwi) is called an "official medicine" in Chinese folk medicine. Puerarin is the main active component extracted from kudzu root, and its structural formula is 8-ß-D-grapes pyranose-4, 7-dihydroxy isoflavone, with a white needle crystal; it is slightly soluble in water, and its aqueous solution is colorless or light yellow. Puerarin is a natural antioxidant with high health value and has a series of biological activities such as antioxidation, anti-inflammation, anti-tumor effects, immunity improvement, and cardio-cerebrovascular and nerve cell protection. In particular, for the past few years, it has also been extensively used in clinical study. This review focuses on the antioxidant activity of puerarin, the therapy of diverse types of inflammatory diseases, various new drug delivery systems of puerarin, the "structure-activity relationship" of puerarin and its derivatives, and pharmacokinetic and clinical studies, which can provide a new perspective for the puerarin-related drug research and development, clinical application, and further development and utilization.

The potential of drug delivery nanosystems to treat COVID-19

The current COVID-19 pandemic demands the rapid development of vaccines and the rapid evaluation of drugs to combat SARS-CoV-2. The urgency of the former ended up in the rapid approval of several vaccines under an emergency use. Despite this, for the latter there is still limited information that successfully demonstrates the efficacy of a particular drug against SARS-CoV-2. Therefore this chapter is intended to summarize antiviral drugs with activity against enveloped viruses (including SARS-CoV-2) that have been further evaluated as cargo of DDS (drug delivery systems). To the best of our knowledge, drugs with activity against SARS-CoV-2 have not been evaluated as part of DDS. The activity of some drugs against COVID-19 has been demonstrated with experiments or computational studies. The antiviral drugs presented are chloroquine, ivermectin, lopinavir/ritonavir, ribavirin, and sofosbuvir. Small interfering RNA (siRNA) is also presented since several DDS carrying siRNA have been evaluated against enveloped viruses. Dexamethasone is a special case that is also presented here as antiinflammatory agent since it is currently used in the treatment of COVID-19. The materials used to produce DDS are diverse and include gelatin, poly(l-lactide), poly(lactic acid), poly(lactic-co-glycolic acid), liposomes, mesoporous silica, and chitosan. © 2022 Elsevier Inc. All rights reserved.