Current Drug Delivery - Volume 19, Issue 8, 2022

Developing 3D living systems will open many doors and lead to significant improvements in biological tools, drug discovery process, lead identification as well as therapeutic approaches. The miniaturization of this approach allows one to perform many more experiments than previously possible more simply. 3D in vitro technology aims to develop a set of tools that are simple, inexpensive, portable, and robust that could be commercialized and used in various fields of biomedical sciences, such as drug discovery, diagnostic tools, therapeutic approaches, and regenerative medicine.

Brain tumors are nothing but a collection of neoplasms that originate either from areas within the brain or from systemic metastasized tumors of other organs spread to the brain. It is a leading cause of death worldwide. The presence of the blood-brain barrier (BBB), blood-brain tumor barrier (BBTB), and some other factors may limit the entry of many potential therapeutics into the brain tissues in the tumor area at the therapeutic concentration required for satisfying effectiveness. Liposomes play an active role in delivering many drugs through BBB into the tumor due to their nanosize and physiological compatibility. The surface of the liposomes can be modified with various ligands that are very specific to the numerous receptors overexpressed onto the BBB as well as onto the diseased tumor surface site (i.e., BBTB) to deliver selective drugs into the tumor site. Further, this colloidal carrier can encapsulate both lipophilic and hydrophilic drugs due to its unique structure. Moreover, the enhanced permeability and retention (EPR) effect can be an added advantage for nanosize liposomes to concentrate into the tumor microenvironment through relatively leaky vasculature of solid tumor in the brain where no penetration restriction applies compared to normal BBB. Here in this review, we have tried to compile the recent advancement along with the associated challenges of liposomes containing different anti-cancer chemotherapeutics across the BBB/BBTB for the treatment of gliomas that will be very helpful for the readers for better understanding of different trends of brain tumor targeted liposomes-based drug delivery and for pursuing fruitful research on the similar research domain.

Tuberculosis (TB) is an ancient chronic disease caused by the bacillus Mycobacterium tuberculosis, which has affected mankind for more than 4,000 years. Compliance with the standard conventional treatment can assure recovery from tuberculosis, but the emergence of drug-resistant strains poses a great challenge for the effective management of tuberculosis. The process of discovery and development of new therapeutic entities with better specificity and efficacy is unpredictable and time-consuming. Hence, delivery of pre-existing drugs with improved targetability is the need of the hour. Enhanced delivery and targetability can ascertain improved bioavailability, reduced toxicity, decreased frequency of dosing and therefore better patient compliance. Nanoformulations are being explored for effective delivery of therapeutic agents, however, optimum specificity is not guaranteed. In order to achieve specificity, ligands specific to receptors or cellular components of macrophage and Mycobacteria can be conjugated to nanocarriers. This approach can improve localization of existing drug molecules at the intramacrophageal site where the parasites reside, improve targeting to the unique cell wall structure of Mycobacterium or improve adhesion to the epithelial surface of intestine or alveolar tissue (lectins). The present review focuses on the investigation of various ligands like Mannose, Mycolic acid, Lectin, Aptamers, etc., installed nanocarriers that are being envisaged for targeting antitubercular drugs.

Background: Opioid medications are an integral part of the management of acute and chronic severe pain. However, non-medical practice of these prescription drug products is emerging as a serious public health problem. To control this opioid epidemic, USFDA is encouraging pharmaceutical companies to develop Abuse Deterrent Formulations (ADFs). ADF's are much more difficult to manipulate and abuse when compared to their conventional formulations. This feature of ADFs is due to their ability to incumber extraction of active ingredients, to prevent administration through alternative routes, making abuse of altered product less rewarding. Objective: The main objective of this review is to abridge different ADFs and various laboratory- based in vitro manipulation and extraction studies, demonstrating that these approved ADFs have the capabilities to deter abuse. Methods: The method includes the collection of data from different search engines like PubMed, FDA guidance documents, ScienceDirect, Google Patents to get coverage of literature in order to get appropriate information regarding ADFs. Results: Various in vitro studies demonstrate that ADFs are effective in minimizing opioid drug abuse, including opioid overdose. However, real impact of these ADFs on reducing the drug abuse can be concluded only after receiving the post marketing data. Conclusion: ADFs are embracing fundamentally different paradigms in the management of severe pain. We believe that the development of abuse deterrent technologies would shift the architype, deterring multipill abuse and can prove as a breakthrough strategy in controlling this opioid epidemic menace.

Alzheimer's Disease (AD) is one of the most important neurodegenerative diseases, accounting for 60% of all dementia cases. AD is a progressive neurodegenerative disease that occurs due to the production of β-amyloid (Aβ) protein and accumulation of hyper-phosphorylated tau protein; it causes breakage in the synaptic bonds and neuronal deaths to a large extent. Millions of people worldwide suffer from AD because there is no definitive drug for disease prevention, treatment, or slowing down its progression. Over the last decade, multiple target applications have been developed for AD treatments. These targets include Aβ accumulations, hyper-phosphorylated tau proteins, mitochondrial dysfunction, and oxidative stress, resulting in toxicity. Various natural or semisynthetic antioxidant formulations have been shown to protect brain cells from Aβ-induced toxicity and provide promising potentials for AD treatment. Ferulic acid (FA), a high-capacity antioxidant molecule, is naturally synthesized from certain plants. FA has been shown to have different substantial biological properties, such as anticancer, antidiabetic, antimicrobial, anti-inflammatory, hepatoprotective, and cardioprotective actions, etc. Furthermore, FA exerts neuroprotection via preventing Aβ-fibril formation, acting as an anti-inflammatory agent, and inhibiting free radical generation and acetylcholinesterase (AChE) enzyme activity. In this review, we present key biological roles of FA and several FA derivatives in preventing Aβ-induced neurotoxicity, protecting against free radical attacks, and exhibiting enzyme inhibitions and evaluate them as possible therapeutic agents for the treatment of AD.

Aim: In this work, the aim was to study the effect of the chain length of surfactant on the self emulsifying system of a poorly soluble drug, aceclofenac. The selection of almond oil as a lipid vehicle was done on the basis of solubility and compatibility of the vehicle with the drug. Methods: The effect of varying chain length of different surfactants of Tween series, namely Tween 20, Tween 40, Tween 60 and Tween 80, was evaluated on self emulsifying efficiency by constructing the pseudoternary diagrams. PEG-400 was used as a co-surfactant in a definite ratio with all the surfactants to minimize their concentration. The best self emulsifying ability was exhibited by Tween 80: PEG-400 combination followed by Tween 60: PEG-400, Tween 40: PEG-400, Tween 20: PEG-400. This observation indicates that as the chain length of Tweens increases, their ability to form a good microemulsion increases if the same co-surfactant is used. Results: However, it has also been found that the presence of unsaturated bond in Tween 80 provides it an elasticity which supports good intermixing of oil and water, leading to formation of a fine microemulsion. Six different formulations were prepared using a combination of almond oil, Tween 80, PEG-400 and the drug aceclofenac. Conclusion: The formulations were subjected to various evaluation parameters, such as dispersibility, transmittance, pH, globule size, polydispersibility, zeta potential, viscosity, refractive index and in vitro dissolution. The best formulation was found to have globule size of less than 100 nm and zeta potential of -3.35 ± 0.60 mV, indicating the formation of a microemulsion of aceclofenac with good stability.

Aim: The aim of the study was to develop a new nano-delivery system for buccal administration of insulin. Background: Biodegradable polymeric nanoparticles (PNPs) had undergone countless breakthroughs in drug delivery systems. The main objective of PNPs application in delivering and carrying different promising drugs is to make sure that the drugs are being delivered to their action sites, maximizing the desired effect and overcoming their limitations and drawbacks. Objective: The main goals of this study were to produce an insulin consumable nano-delivery system for buccal administration and enhance the mucoadhesive effect in sustaining insulin release. Methods: Water-oil-water (W-O-W) microemulsion solvent evaporation technique was used for the preparation of nanoparticles consisting of positively charged poly (D, L-lactide-co-glycolide) coated with chitosan and loaded with insulin. Later, a consumable buccal film was prepared by the spin coating method and loaded with the previously prepared nanoparticles. Results: The newly prepared nanoparticle was assessed in terms of size, charge and surface morphology using a Scanning Electron Microscope (SEM), zeta potential, Atomic Force Microscope (AFM), and Fourier Transform Infra-red (FTIR) spectroscopy. An in vitro investigation of the insulin release from nanoparticles and buccal film demonstrated controlled as well as sustained delivery over 6 hrs. The cumulative insulin release decreased to about 28.9% with buccal film compared to the nanoparticle (50%). Conclusion: The buccal film acted as a barrier for insulin release. Therefore, the release was sustained.