Recent advances in drug delivery and formulation最新文献

The term "reactive oxygen species" (ROS) refers to a family of extremely reactive molecules. They are crucial as secondary messengers in both physiological functioning and the development of cancer. Tumors have developed the ability to survive at elevated ROS levels with significantly higher H2O2 levels than normal tissues. Chemodynamic therapy is a novel approach to cancer treatment that generates highly toxic hydroxyl radicals via a Fenton/Fenton-like reaction between metals and peroxides. Inorganic nanoparticles cause cytotoxicity by releasing ROS. Inorganic nanoparticles can alter redox homoeostasis by generating ROS or diminishing scavenging mechanisms. Internalized nanoparticles generate ROS in biological systems independent of the route of internalisation. This method of producing ROS could be employed to kill cancer cells as a therapeutic strategy. ROS also play a role in regulating the development of normal stem cells, as excessive ROS disturb the stem cells' regular biological cycles. ROS treatment has a significant effect on normal cellular function. Mitochondrial ROS are at the centre of metabolic changes and control a variety of other cellular processes, which can lead to medication resistance in cancer patients. As a result, utilising ROS in therapeutic applications can be a double-edged sword that requires better understanding.

Vaccines are one of the greatest medical achievements of modern medicine. The nasal mucosa represents an effective route of vaccination for both mucosal immunity and peripheral, being at the same time an inductive and effector site of immunity. In this paper, the innovative and patented compositions and manufacturing procedures of nanomaterials have been studied using the peerreviewed research literature. Nanomaterials have several properties that make them unique as adjuvant for vaccines. Nanoadjuvants through the influence of antigen availability over time affect the immune response. Namely, the amount of antigen reaching the immune system or its release over prolonged periods of time can be effectively increased by nanoadjuvants. Mucosal vaccines are an interesting alternative for immunization of diseases in which pathogens access the body through these epithelia. Nanometric adjuvants are not only a viable approach to improve the efficacy of nasal vaccines but in most of the cases they represent the core of the intellectual property related to the innovative vaccine.

Background: The oral route is a highly recommended route for the delivery of a drug. But most lipophilic drugs are difficult to deliver via this route due to their low aqueous solubility. Selfemulsifying drug delivery systems (SEDDS) have emerged as a potential approach of increasing dissolution of a hydrophobic drug due to spontaneous dispersion in micron or nano sized globules in the GI tract under mild agitation.

Objective: The main motive of this review article is to describe the mechanisms, advantages, disadvantages, factors affecting, effects of excipients, possible mechanisms of enhancing bioavailability, and evaluation of self-emulsifying drug delivery systems.

Results: Self emulsifying systems incorporate the hydrophobic drug inside the oil globules, and a monolayer is formed by surfactants to provide the low interfacial tension, which leads to improvement in the dissolution rate of hydrophobic drugs. The globule size of self-emulsifying systems depends upon the type and ratio of excipients in which they are used. The ternary phase diagram is constructed to find out the range of concentration of excipients used. This review article also presents recent and updated patents on self-emulsifying drug delivery systems. Self-emulsifying systems have the ability to enhance the oral bioavailability and solubility of lipophilic drugs.

Conclusion: This technique offers further advantages such as bypassing the first pass metabolism via absorption of drugs through the lymphatic system, easy manufacturing, reducing enzymatic hydrolysis, inter and intra subject variability, and food effects.

Background: Infectious diseases have the highest mortality rate in the world and these numbers are associated with scarce and/or ineffective diagnosis and bacterial resistance. Currently, with the development of new pharmaceutical formulations, nanotechnology is gaining prominence.

Methods: Nanomicelles were produced by ultrasonication. The particle size and shape were evaluated by scanning electron microscopy and confirmed by dynamic light scattering, also thermogravimetric analysis was performed to evaluate the thermal stability. Finally, antibacterial activity has been performed.

Results: The results showed that a rod-shaped nanosystem, with 316.1 nm and PDI of 0.243 was formed. The nanosystem was efficient against Staphylococcus aureus, Pseudomonas aeruginosa, and Bacillus subtilis subsp. spizizenii with MIC inferior to 0.98 and a synergistic effect between silver graphene quantum dots and levofloxacin was observed.

Conclusion: The nanosystem produced may rise as a promising agent against the bacterial threat, especially regarding bacterial resistance.

Background: Transfersomes can be used to enhance transdermal drug delivery due to their flexibility and ability to incorporate various molecules. For example, hydrocortisone (HC), a corticosteroid, is taken by different routes and serves as immunosuppressive, anticancer, and antiallergenic; however, it is poorly absorbed by the skin.

Objective: Therefore, the current study suggested HC-loaded transfersomes as an alternative route of administration for reaching deeper skin layers or systemic circulation, to reduce the side effects of HC and improve its bioavailability.

Methods: HC transfersomes were prepared by the thin-film hydration method and characterized for their vesicular size, zeta potential, drug entrapment efficiency, elasticity, FTIR spectroscopy, in vitro drug release, ex vivo permeation, and irritancy in rabbits. The optimized formulation, F15 (containing HC 20 mg, egg phosphatidylcholine (EPC) 400 mg, and 75 mg of Span 80), was chosen because it showed the highest (p< 0.05) EE% (60.4±0.80) and optimized sustained in vitro drug release (Q8 = 87.9±0.6%).

Results: Extensive analysis of the drug release data from all formulas was performed using the DDSolver software which quantitatively confirmed the successful formulation. The Weibull equation was the best model to fit the release data compared to others, and the release mechanism was Fickian diffusion.

Conclusion: The simulated pharmacokinetic parameters showed that F15 had the highest AUC, MDT, and DE. Furthermore, F15 significantly enhanced HC permeation by 12-folds compared to the control through the excised rat's skin. The skin irritancy test has proven F15 safety and skin compatibility.

Introduction: Serious COVID-19 respiratory problems start when the virus reaches the alveolar level, where type II cells get infected and die. Therefore, virus inhibition at the alveolar level would help preventing these respiratory complications.

Method: A literature search was conducted to collect physicochemical properties of small molecule compounds that could be used for the COVID-19 treatment. Compounds with low melting points were selected along with those soluble in ethanol, hydrogen-bond donors, and acceptors.

Results: There are severe acute respiratory syndrome coronavirus inhibitors with physicochemical properties suitable for the formulation as an ultrafine pressurised metered-dose inhaler (pMDI). Mycophenolic acid, Debio 025, and cyclosporine A are prime candidates among these compounds. Cyclosporine A (hereafter cyclosporine) is a potent SARS-CoV-2 inhibitor, and it has been used for the treatment of COVID-19 patients, demonstrating an improved survival rate. Also, inhalation therapy of nebulised cyclosporine was tolerated, which was used for patients with lung transplants. Finally, cyclosporine has been formulated as a solution ultrafine pMDI. Although vaccine therapy has started in most countries, inhalation therapies with non-immunological activities could minimise the spread of the disease and be used in vaccine-hesitant individuals.

Conclusion: Ultrafine pMDI formulation of cyclosporine or Debio 025 should be investigated for the inhalation therapy of COVID-19.

Pharmaceutical oral dosage forms are tremendously preferred by both consumers as well as pharmaceutical manufacturers owing to the plethora of benefits they offer. Lozenges (LZs) are one of the dosage forms that provide a palatable means of drug administration and have great importance with respect to their pharmaceutical applications. LZs offer additional benefits to pediatric and geriatric patients, along with people having problems associated with the gastro-intestinal tract. Dysphagia is a common problem faced by all age groups, which gives rise to the need for LZs. Moreover, the foremost merit presented by the medicated LZs includes its augmented retention time in the oral cavity that results in an enhanced bioavailability for buccal or upper gastro-intestinal disorders. Further, LZs can also be used to bypass the first-pass effect. The present review covers various aspects of LZs such as formulation, manufacturing techniques, evaluation parameters, marketed products, patents, and a compilation of research work that has been done on lozenges as a delivery system.

L-asparaginase (L-asparagine amino hydrolase, E.C.3.5.1.1) is the most important chemotherapeutic drug used in treating Acute Lymphocytic Leukemia (ALL), decreasing blood asparagine rates causing apoptosis in tumor cells. However, pharmacological drugs cause several side effects making treatments difficult. Thus, searches for new sources of L-asparaginase or enzyme modifications focus on discovering new products to use in therapy. This article reviewed published patents from 2000 to 2020 related to the treatment of ALL using L-asparaginase. Many organisms have been shown as potential viable L-asparaginase producers for use in the treatment of ALL. However, this patent review shows that few of these organisms are gaining attention to becoming bioproducts for the market. It is expected that drugs in the testing phase and patents related to the treatment of ALL and other cancers will become real products. Besides, a treatment using an amino acid depletion approach, now referring to asparagine, altogether with a compound that directly interferes with the expression of the asparagine synthase gene, is more suitable for the treatment of ALL and possibly to other cancers.

At the present time, designing of defined release dosage forms, either controlled, sustained, modified, are gaining much importance. For the development of such delivery systems, proper blend of polymers is required so that drug release occurs by polymer erosion, swelling, diffusion/ dissolution. HPMC (Hydroxypropyl Methylcellulose) is the most commonly used cellulosic polymer available in various grades to develop such types of systems. Depending upon the molecular weight and viscosity chosen, it can be applied for emulsification, adhesion, bonding, thickening, suspension, film forming and gelation. It consists of polymeric units linked together, which retain water, thereby acting as an excellent hydrophilic gel forming polymer. It generally hydrates on the outer surface to form a gelatinous layer. It swells, expands upon contact with water and releases the drug in predetermined manner initially and then forms viscous gel to control the release further. The objective of the present review is to overview the recent patents and articles of HPMC, its properties, grades and its use in various drug delivery systems and as a binder, dispersing agent, bioavailability enhancer and as capsule forming material have been identified and reviewed.

Co-crystal is an attractive alternative and a new class of solid forms because that can be engineered to have desired physicochemical properties. Co-crystals have gained considerable attention from the generic pharmaceutical industry after the USFDA released its finalized guidlines in the year 2018 on the regulatory classification of co-crystals. In this review, we discussed how co-crystals could be explored as a potential alternative solid form for the development of a generic product that meets the legal, regulatory, and bioequivalence requirements. In the contents, we discussed in detail concepts such as the selection of coformers, various ways of making co-crystals, the strategy of characterization to discriminate between co-crystal and salt, polymorphism in co-crystals, the aspects of intellectual property and, finally, the regulatory aspects of co-crystals.