Current Drug Delivery - Volume 18, Issue 2, 2021

Lung cancer is the second most diagnosed cancer in both men and women worldwide. Considering the high mortality rate of lung cancer and inadequacy of conventional treatment methods such as surgical resection, chemotherapy and radiotherapy; new treatment strategies are an emerging area of interest. Nanoparticle-based drug and small interfering RNA delivery systems such as lipid, polymeric, inorganic, micellar and dendrimer nanoparticles are designed to enhance the bioavailability, stability and retention of anti-cancer drugs in the targeted regions of the lung. These nanoparticle-based delivery systems increase the active ingredient half-life and targeting efficiency while reducing the required dose of the drug. Hence, they have many advantages such as higher therapeutic efficacy and reducedside effects and adverse events. Combinations of active ingredients, anti-cancer agents and small interfering RNA can be formulated into nanoparticle-based delivery systems that can be administered by various routes including inhalation and intravenous. In this review, the development of lipidic and polymeric nanoparticle-based drug and small interfering RNA delivery systems used in the treatment of lung cancer is discussed.

Migraine is a chronic, painful, neurological disorder that affects approximately 15% of the population worldwide. It is a form of neurovascular headache: a disorder in which neural events result in the dilation of blood vessels that, in turn, results in pain and further nerve activation. The pathogenesis of migraine is not completely understood, but it is thought that both central and peripheral stimulations can play a role in migraine. Experimental pharmacological evidence suggests that some drugs can have actions in migraine treatment and oral drug delivery is the first choice for these drugs. However, the oral absorption of many drugs is delayed during migraine attacks. Therefore, there may be an advantage to other drug delivery routes, such as parenteral and intranasal. Moreover, nanoparticles can be used for improved drug delivery of anti-migraine agents as they can protect the encapsulated drug from biological and/or chemical degradation, and extracellular transport by P-gp efflux proteins. Various analytical studies have been performed to sensitive and selective assays of antimigraine drugs from commercial and real samples. Anti-migraines, either single or combined with other drugs, can be easily detected by several analytical methods, such as ultraviolet spectrometry, visible spectrometry, high-performance liquid chromatography, liquid chromatography-mass spectrometry, and high-performance thin layer chromatography. This review focuses on the status of antimigraine drug delivery technologies and possible routes for drug delivery. Moreover, it will present their analytical assays with different methods.

Currently, despite many active compounds have been introduced to the treatment, cancer remains one of the most vital causes of mortality and reduced quality of life. Conventional cancer treatments may have undesirable consequences due to the continuous differentiating, dynamic and heterogeneous nature of cancer. Recent advances in the field of cancer treatment have promoted the development of several novel nanoformulations. Among them, the lipid coated nanosized drug delivery systems have gained an increasing attention by the researchers in this field owing to the attractive properties such as high stability and biocompatibility, prolonged circulation time, high drug loading capacity and superior in vivo efficacy. They possess the advantages of both the liposomes and polymeric nanoparticles which makes them a chosen one in the field of drug delivery and targeting. Core-shell type lipid-coated nanoparticle systems, which provide the most prominent advantages of both liposomes such as biocompatibility and polymeric/inorganic nanoparticles such as mechanic properties, offer a new approach to cancer treatment. This review discusses design and production procedures used to prepare lipid-coated nanoparticle drug delivery systems, their advantages and multifunctional role in cancer therapy and diagnosis, as well as the applications they have been used in.

Drug abuse is considered a serious source of economic and social problems. The identification of drugs of abuse is in demand in forensic and clinical toxicology. There are various methods for the determination of these materials, including chromatographic and mass spectrometric techniques. However, most of these techniques need high-cost equipment, they are time-consuming, and they suffer from complicated sample preparation protocols. In contrast, electrochemical methods are low cost, mobile, and they do not require complicated sample preparation protocols. The use of nanomaterials in electroanalysis has gained significant attention in order to improve selectivity, enhance sensitivity, and lower the limit of detections. Nanomaterials have significantly gained research-interest due to their low cost (due to low amounts of materials being used) and their uniquely size-dependent properties. The incorporation of nanomaterials into host matrices is important to prepare nanocomposite sensor films. Unique properties of nanomaterials and hybrid materials, such as mechanical strength, electrical conductivity, optical responsiveness, specific catalytic and magnetic properties, in addition to high surface area per mass ratio are attractive. Besides providing novel properties, nanomaterials allow low-cost electrode fabrication based on simple technologies. The combination of nanotechnology with modern electroanalytical techniques allows innovation in electrical sensing devices with features like increased mass transport, high sensor surface area, and controlled electrode surface micro-environment. The aim of this review is to give an outline of electroanalytical determination based on nanomaterials focusing on illicit drugs in matrices, such as urine, blood, or saliva. We summarize developments in field-based sensors for determining drugs of abuse.

Aims: The study aimed at developing and characterizing Nanostructured Lipid Carriers (NLC) of Quetiapine Fumarate (QF) by Design of Experiment (DoE) for the enhancement of bioavailability.

Background: QF, an anti-psychotic drug, has an oral bioavailability of 9% due to hepatic first- pass metabolism necessitating the use of high doses. Its side effects are dose -related and enhancement in bioavailability would result in minimization of side effects.

Objective: The objective of the study was the enhancement of bioavailability of the NLC of QF by preferential lymphatic uptake.

Methods: Hot emulsification-ultrasonication was the method of formulation using PrecirolATO5 and Oleic acid as solid and liquid lipids respectively. Poloxamer188 and Phospholipon90G were used as surfactant and stabilizer respectively. Solid:liquid lipid ratio and Phospholipon90G amount were independent variables and percent Entrapment Efficiency (%EE), Particle Size (PS) dependent variables during optimization by Central Composite Design.

Results: The optimized formulation showed a %EE of 77.21%, PS of 140.2 nm and surface charge of - 19.9mV. Higuchi kinetic model was followed during the in-vitro release. TEM revealed spherical, smooth nanoparticles. A pharmacokinetic study in rats showed AUC0-∞ of QF-NLC to be 3.93 times that of QF in suspension, suggesting significant enhancement in bioavailability. An increase in AUC0-∞ in cycloheximide untreated rats’ group of QF-NLC by 2.43 times as compared to cycloheximide treated group, confirmed lymphatic absorption of QF- NLC.

Conclusion: The results validated DoE as an appropriate tool for developing QF loaded NLC and proved NLC to be a promising delivery system for the enhancement of oral bioavailability of QF.

Background: Oral mucositis, one of the most common complications of 5-Fluorouracil (5-FU) treatment, leads to several problems, including pain, diarrhea and malnutrition, and reduces the quality of life and subsequent treatments. Melatonin, a neurohormone with anti-inflammatory and antioxidant activities, was encapsulated in niosomes and embedded in a mucoadhesive gel formulation as a Melatonin Niosome Gel (MNG) to perform oral mucositis treatment. Objective: This study aimed to investigate the effectiveness of MNG for the treatment of 5-FU-induced oral mucositis in mice. Methods: Oral mucositis was induced in ICR mice by 5-FU and randomly assigned to receive daily applications of the topical oral MNG, a fluocinolone acetonide gel, a blank niosome gel, or no treatment for 5 days in comparison with a normal group. Average body weights, food consumption, and behaviors of the mice as well as microscopic histopathology, Fourier-Transform Infrared Spectroscopy (FTIR) analysis, proinflammatory cytokine levels, and oxidative stress markers of the tongues were monitored and collected after sacrifice. Results: In comparison to the normal group, the average body weights of the 5-FU-MNG mice did not deviate from that of the normal group, nor was there a significant difference in the time to sleep or licking (p>0.05 for both parameters). In addition, the mice treated with MNG and fluocinolone acetonide did not show significantly different histopathological, FTIR, interleukin-1β or malondialdehyde (MDA) results in the tongues used as the oral tissue samples. Conclusion: Topical MNG potentially inhibits inflammation and lipid oxidative stress in 5-FU-induced oral mucositis.

Background: Betulinic Acid (BA) is a lipophilic compound with proven beneficial results in topical inflammation. Nanogels (NG) are carriers of bioactive compounds with properties that make them good candidates to treat skin diseases. Objective: The objective of this study was to evaluate the anti-inflammatory activity of BA carried in NG. Methods: NG were composed of a nanoemulsion and a crosslinking agent (Carbopol 940^®) applied at three concentrations (0.5, 1, and 1.5 %) and three activation times (6, 12 and 24 h). In order to select the optimal formulation, the NG were characterized mechanically and micro-structurally followed by evaluation of the BA anti-inflammatory activity in an in vivo model of auricular edema. We determined the edema inhibition activity as percent weight. Additionally, the anti-inflammatory activity of NG was validated through histological analysis. Results: The formulation with the best viscoelastic properties was the one prepared with 0.5% carbopol and 6 h of activation. Microstructural examination of this formulation showed mostly spherical structures with a mean diameter of 65 nm. From the evaluation of edema and the histological analyses, we established that the NG of BA produced 52% inhibition. In contrast, a conventional gel and free BA produced 28% and 19% inhibition, respectively. Conclusion: The NG of BA were found to be good vehicles to treat skin inflammation.

Objective: A ceftiofur hydrochloride long-acting oily suspension with no irritation was prepared by testing and optimizing the types and amounts of organic solvents, suspending agents, and surfactants. Methods: Its properties, stability, injection site irritation, in vitro release, and pharmacokinetics in pigs were evaluated. The optimum formulation was used ethyl oleate, aluminum monosterate, and span-80 as organic solvents, suspending agents, and surfactant, respectively. The drug microparticles were uniform long strip with size of 1.53 ± 0.11 μm and no agglomerations, and were evenly dispersed. The re-dispersed time, sedimentation rate and pH value of the suspension were 4 s under a magnetic shaker rotating at 20 r/min, 1 and 5.0, respectively. It could go through 7-gage needle smoothly with withdrawal volume of 9.9 mL/min. Results: The suspension showed good stability when stored away from light, no irritation at the injection site and sustained release in PBS buffer. After intramuscular administration, the drug concentration above 0.15 μg/mL was last for 120 h. Its elimination half-life (T1/2ke), mean residence time (MRT), and bioavailability were increased by 1.73, 1.62, and 2.16 times compared to Excenel^®. Conclusion: The results suggested that the suspension had excellent sustained-release and will make ceftiofur hydrochloride more effective and convenient to use.

Objective: This study aimed to fabricate Hyaluronic Acid (HA)/parecoxib-loaded PLGA microspheres for the treatment of Temporomandibular Disorders (TMD) and investigate the in vitro and in vivo effect of the microsphere system to solve the issues of poor drug delivery and short duration on drug concentration in conventional TMD therapy. Methods: The microspheres were prepared by the double emulsion (w/o/w) method. Various formulations were compared in terms of particle size, drug loading rate and encapsulation rate. Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC) and FT-IR spectroscopy were performed to evaluate physicochemical properties. The drug release behavior of microspheres and toxicity assay on synovial cells were investigated. The in vitro anti-inflammatory effect on inflammatory markers, such as IL-1β, TNF-α and COX-2, was assessed by real-time PCR. Then, the in vivo therapeutic effect of microspheres was investigated using mechanically-induced rat synovitis model. Protein levels of inflammatory cytokines (IL-1β, TNF-α and COX-2) from TMJ periarticular tissues were quantified by Enzyme-Linked Immunosorbent Assay (ELISA). Results: The results showed that microspheres were morphologically regular, smooth and non-cohesive. The average particle size of the microspheres was (25.32 ± 1.01) μm. The drug loading rate of parecoxib was 17.12%-20.95% with encapsulation efficiency reaching 51.9%-54.7%. in vitro drug release tests showed a successful sustained release over 28 days with a burst of 19.98% of the total drug substance. Treatment with HA/parecoxib-loaded PLGA microspheres declined the mRNA expression of IL-1β, TNF-α and COX-2 induced by LPS in articular synovial cells. Moreover, in vivo results demonstrated that the intra-articular microspheres significantly reduced protein levels of inflammatory cytokines (IL-1β, TNF-α and COX-2) for more than two weeks and stopped the mechanically-induced synovitis in its tracks in rat models. Conclusion: The study presented new and potential insights into treatments of TMD using PLGA microspheres loaded with HA and parecoxib as a successful drug delivery system.