Microneedle-Based Vaccine Delivery: Review of an Emerging Technology.

Vaccination has produced a great improvement to the global health by decreasing/eradicating many infectious diseases responsible for significant morbidity and mortality. Thanks to vaccines, many infections affecting childhood have been greatly decreased or even eradicated (smallpox, measles, and polio). That is why great efforts are made to achieve mass vaccination against COVID-19. However, developed vaccines face many challenges with regard to their safety and stability. Moreover, needle phobia could prevent a significant proportion of the population from receiving vaccines. In this context, microneedles (MNs) could potentially present a solution to address these challenges. MNs represent single dose administration systems that do not need reconstitution or cold-chain storage. Being self-administered, pain-free, and capable of producing superior immunogenicity makes them a more attractive alternative. This review explores microneedles' types, safety, and efficacy in vaccine delivery. Preclinical and clinical studies for microneedle-based vaccines are discussed and patent examples are included.

Formulation, optimization, and evaluation of raft-forming formulations containing Nizatidine.

OBJECTIVE: The main objective of this research is to formulate, optimize, and evaluate raft-forming chewable tablets of Nizatidine. Various raft-forming agents were used in preliminary screening. Sodium alginate showed maximum raft strength, so tablets were prepared using sodium alginate as the raft forming agent, along with calcium carbonate (CaCO3) as antacid and raft strengthening agent, and sodium bicarbonate (NaHCO3) as a gas generating agent. RESEARCH DESIGN AND METHODS: Raft forming chewable tablets containing Nizatidine were prepared by direct compression and wet granulation methods, and evaluated for drug content, acid neutralization capacity, raft strength, and in-vitro drug release in 0.1 N HCl. Box-Behnken design was used for optimization. RESULTS: Two optimized formulations were predicted from the design space. The first optimized recommended concentrations of the independent variables were predicted to be X1 = 275.92 mg, X2 = 28.60 mg, and X3 = 202.14 mg for direct compression technique and the second optimized recommended concentrations were predicted to be X1 = 253.62 mg, X2 = 24.60 mg, and X3 = 201.77 mg for wet granulation technique. Optimized formulations were stable at accelerated environmental testing for six months at 35 °C and 45 °C with 75% relative humidity. X-Ray showed that the raft floated immediately after ingestion and remained intact for ∼3 h. CONCLUSION: Raft was successfully formed and optimized. Upon chewing tablets, a raft is formed on stomach content. That results in rapid relief of acid burning symptoms and delivering the drug into systemic circulation with enhanced bioavailability.

Effectiveness of epigallocatechin gallate nanoparticles on the in-vivo treatment of Alzheimer's disease in a rat/mouse model: a systematic review.

BACKGROUND: Alzheimer's disease (AD) is a neurological disease that causes memory loss over time. Current therapies are limited and frequently inadequate. Epigallocatechin gallate (EGCG), has antioxidant, anti-inflammatory, antifibrosis, anti-remodeling and tissue-protective qualities that may be effective in treatment of different diseases, including AD. Because of nanoparticles' high surface area, they can enhance solubility, stability, pharmacokinetics and biodistribution, and diminish toxicities. Besides, lipid nanoparticles have a high binding affinity that can enhance the rate of drug transport across BBB. So, EGCG nanoparticles represent a promising treatment for AD. OBJECTIVES: This systematic review sought to assess the efficacy of EGCG nanoparticles against AD in rat/mouse models. METHODS: Study was conducted in accordance with PRISMA guidelines, and the protocol was registered in PROSPERO. Electronic databases were searched to discover relevant studies published up to October 2022. RESULTS: Two studies met the inclusion criteria out of 1338 and were included in this systematic review. Collectively, the results indicate that EGCG has a significant potential for reducing AD pathology and improving cognitive deficits in rat/mouse models. The formulated particles were in the nanometer range, as indicated by TEM, with good particle size control and stability. EGCG nanoparticles showed superior pharmacokinetic characteristics and improved blood-brain barrier permeability, and increased brain bioavailability compared to free EGCG. Additionally, nanoEGCG were more effective in modulating oxidative stress than free formulation and decreased AChE in the cortex and hippocampus of AlCl3-treated rats. CONCLUSION: This systematic analysis of the two studies included showed that EGCG nanoparticles are efficacious as a potential therapeutic intervention for AD in rat/mouse models. However, limited number of studies found indicates insufficient data in this research point that requires further investigation by experimental studies.

Optimized Nanoparticles for Enhanced Oral Bioavailability of a Poorly Soluble Drug: Solid Lipid Nanoparticles Versus Nanostructured Lipid Carriers.

INTRODUCTION: Rosuvastatin calcium (ROSCa) is an anti-hyperlipidemic drug with only 20% oral bioavailability due to its low solubility and high first-pass metabolism. Therefore, the main purpose of this work was to compare solid lipid nanoparticles to nanostructured lipid carriers and evaluate their effect on solubility improvement and hence the bioavailability of a model insoluble drug. METHODS: Different nanosuspensions were formulated using high-speed homogenization and ultrasonication techniques, using Apifil as solid lipid and Maisine as liquid lipid. The effect of different variables on quality attributes (particle size, entrapment efficiency (EE), and in vitro release) was studied using the Box-Behnken design. Then, the optimized nanoparticles were lyophilized, filled into capsules, and evaluated. Finally, the optimized formula was clinically evaluated in six healthy human volunteers. RESULTS: It was observed that the variables had a great impact on EE and particle size. Nanoparticles showed maximum particles of 180.3 nm, and % EE ranged from 40.77% to 91.67%. Capsules loaded with NLCs were found to be more stable than those loaded with SLNs. The clinical study of NLCs-ROSCa showed an enhancement in the C max (8.92 ng/ml) compared to the commercial product (2.56 ng/ml) with approximately 349% relative bioavailability. CONCLUSION: ROSCa was successfully encapsulated in SLNs and NLCs. The optimized NLCs formulation showed improved quality attributes compared to SLNs. Thus, NLCs loaded formulations could be an effective oral drug delivery system to enhance the bioavailability of insoluble drugs.

3D-Printed Microfluidics Potential in Combating Future and Current Pandemics (COVID-19).

Coronavirus disease (COVID-19) emerged in China in December 2019. In March 2020, the WHO declared it a pandemic leading to worldwide lockdowns and travel restrictions. By May, it infected 4,789,205 and killed 318,789 people. This led to severe shortages in the medical sector besides devastating socio-economic effects. Many technologies such as artificial intelligence (AI), virtual reality (VR), microfluidics, 3D printing, and 3D scanning can step into contain the virus and hinder its extensive spread. This article aims to explore the potentials of 3D printing and microfluidic in accelerating the diagnosis and monitoring of the disease and fulfilling the shortages of personal protective equipment (PPE) and medical equipment. It highlights the main applications of 3D printers and microfluidics in providing PPE (masks, respirators, face shields, goggles, and isolation chambers/hoods), supportive care (respiratory equipment) and diagnostic supplies (sampling swabs & lab-on-chip) to ease the COVID-19 pressures. Also, the cost of such technology and regulation considerations are addressed. We conclude that 3D printing provided reusable and low-cost solutions to mitigate the shortages. However, safety, sterility, and compatibility with environmental protection standards need to be guaranteed through standardization and assessment by regulatory bodies. Finally, lessons learned from this pandemic can also help the world prepare for upcoming outbreaks.