Transdermal drug delivery (TDD) is a technique that is used to deliver a drug into the systemic circulation across the skin. This mechanism of drug delivery route has many advantages, including steady drug plasma concentrations, improved patient compliance, elimination of hepatic first pass, and degradation in the gastrointestinal tract. Over the last 30 years, many transdermal products have been launched in the market. Despite the inherent advantages of TDD and the growing list of transdermal products, one of the major drawbacks to TDD is the occurrence of inter- and intraindividual variation in the absorption of the drug across the skin. A majority of these variations are caused by biological factors, such as gender, age, ethnicity, and skin hydration and metabolism. These factors affect the integrity and the barrier qualities of the skin, which subsequently result in the variation in the amount of drug absorbed. The main objective of this review article is to provide a concise commentary on the biological factors that contribute to the variation in transdermal permeation of drugs across human skin and the available transdermal therapeutic systems that may reduce the variations caused by biological factors.
The resistant level of the houseflies to six kinds of insecticides, DDT, Resmethrin, DDVP, Baytex, Sumithion and Diazinon, was examined on the seven strains collected in Malaysia. It was found that their susceptibility is rather higher than that of the Takatsuki strain which is a standard strain in Japan. However, their susceptibility to Sumithion was the same or slightly lower than that of the Takatsuki strain. The resistant level to five of six kinds of insecticides was the highest in the strain of Cameron Highland. The values were close to Singh's data in 1973, and this means that the resistance of the houseflies to the insecticides is increasing in Malaysia.
The drawbacks associated with chemical skin permeation enhancers such as skin irritation and toxicity necessitated the research to focus on potential permeation enhancers with a perceived lower toxicity. Crude palm oil (CPO) is obtained by direct compression of the mesocarp of the fruit of the oil palm belonging to the genus Elaeis. In this research, CPO and tocotrienol-rich fraction (TRF) of palm oil were evaluated for the first time as skin permeation enhancers using full-thickness human skin. The in vitro permeation experiments were conducted using excised human skin mounted in static upright 'Franz-type' diffusion cells. The drugs selected to evaluate the enhancing effects of these palm oil derivatives were 5-fluorouracil, lidocaine and ibuprofen: compounds covering a wide range of Log p values. It was demonstrated that CPO and TRF were capable of enhancing the percutaneous permeation of drugs across full-thickness human skin in vitro. Both TRF and CPO were shown to significantly enhance the permeation of ibuprofen with flux values of 30.6 µg/cm2 h and 23.0 µg/cm2 h respectively, compared to the control with a flux of 16.2 µg/cm2 h. The outcome of this research opens further scope for investigation on the transdermal penetration enhancement activity of pure compounds derived from palm oil.
This work reports the comparison of heat-treated and non-heat-treated laminated object-manufactured (LOM) 3D-printed specimens from mechanical and morphological viewpoints. The study suggests that heat treatment of the FDM-printed specimen may have a significant impact on the material characteristics of the polymer. The work has been performed at two stages for the characterization of (a) non-heat-treated samples and (b) heat-treated samples. The results for stage 1 (non-heat-treated samples) suggest that the infill density: 70%, infill pattern: honeycomb, and six number of discs in a single LOM-manufactured sample is the optimized condition with a compression strength of 42.47 MPa. The heat treatment analysis at stage 2 suggests that a high temperature: 65 °C, low time interval: 10 min, works equally well as the low temperature: 55 °C, high time interval: 30 min. The post-heat treatment near Tg (65 °C) for a time interval of 10 min improved the compressive strength by 105.42%.
Introduction: Pulmonary route is one of the preferred routes for the administration of therapeutically active agents for systemic as well as localized delivery. Chronic obstructive pulmonary disease (COPD), bronchial asthma, pneumonia, pulmonary hypertension, bronchiolitis, lung cancer, and tuberculosis are the major chronic diseases associated with the pulmonary system. Knowledge about the affecting factors, namely, the etiology, pathophysiology, and the various barriers (mechanical, chemical, immunological, and behavioral) in pulmonary drug delivery is essential to develop an effective drug delivery system. Formulation strategies and mechanisms of particle deposition in the lungs also play an important role in designing a suitable delivery system.Areas covered: In the present paper, various drug delivery strategies, viz. nanoparticles, microparticles, liposomes, powders, and microemulsions have been discussed systematically, from a patent perspective.Expert opinion: Patent publications on formulation strategies have been instrumental in the evolution of new techniques and technologies for safe and effective treatment of pulmonary diseases. New delivery systems are required to be simple/reproducible/scalable/cost-effective scale for manufacturing ability and should be safe/effective/stable/controllable for meeting quality and regulatory compliance.
Current advancements in nanotechnology and nanoscience have resulted in new nanomaterials, which may pose health and environmental risks. Furthermore, several researchers are working to optimize ecologically friendly procedures for creating metal and metal oxide nanoparticles. The primary goal is to decrease the adverse effects of synthetic processes, their accompanying chemicals, and the resulting complexes. Utilizing various biomaterials for nanoparticle preparation is a beneficial approach in green nanotechnology. Furthermore, using the biological qualities of nature through a variety of activities is an excellent way to achieve this goal. Algae, plants, bacteria, and fungus have been employed to make energy-efficient, low-cost, and nontoxic metallic nanoparticles in the last few decades. Despite the environmental advantages of using green chemistry-based biological synthesis over traditional methods as discussed in this article, there are some unresolved issues such as particle size and shape consistency, reproducibility of the synthesis process, and understanding of the mechanisms involved in producing metallic nanoparticles via biological entities. Consequently, there is a need for further research to analyze and comprehend the real biological synthesis-dependent processes. This is currently an untapped hot research topic that required more investment to properly leverage the green manufacturing of metallic nanoparticles through living entities. The review covers such green methods of synthesizing nanoparticles and their utilization in the scientific world.
Majority of the representative drugs customarily interact with multiple targets manifesting unintended side effects. In addition, drug resistance and over expression of the cellular efflux-pumps render certain classes of drugs ineffective. With only a few innovative formulations in development, it is necessary to identify pharmacophores and novel strategies for creating new drugs. The conjugation of dissimilar pharmacophoric moieties to design hybrid molecules with an attractive therapeutic profile is an emerging paradigm in the contemporary drug development regime. The recent decade witnessed the remarkable biological potential of 1,3,5-triazine framework in the development of various chemotherapeutics. The appending of the 1,3,5-triazine nucleus to biologically relevant moieties has delivered exciting results. The present review focuses on 1,3,5-triazine based hybrid molecules in the development of pharmaceuticals.
Neurons depend on mitochondrial functions for membrane excitability, neurotransmission, and plasticity. Mitochondrial dynamics are important for neural cell maintenance. To maintain mitochondrial homeostasis, lysosomes remove dysfunctional mitochondria through mitophagy. Mitophagy promotes mitochondrial turnover and prevents the accumulation of dysfunctional mitochondria. In many neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), mitophagy is disrupted in neurons. Mitophagy is regulated by several proteins; recently, Rho-associated coiled-coil containing protein kinase 2 (ROCK2) has been suggested to negatively regulate the Parkin-dependent mitophagy pathway. Thus, ROCK2 inhibition may be a promising therapy for NDDs. This review summarizes the mitophagy pathway, the role of ROCK2 in Parkin-dependent mitophagy regulation, and mitophagy impairment in the pathology of AD. We further discuss different ROCK inhibitors (synthetic drugs, natural compounds, and gene therapy-based approaches) and examine their effects on triggering neuronal growth and neuroprotection in AD and other NDDs. This comprehensive overview of the role of ROCK in mitophagy inhibition provides a possible explanation for the significance of ROCK inhibitors in the therapeutic management of AD and other NDDs.