Pharmaceutical Nanotechnology - Volume 12, Issue 1, 2024

Exosomes are intrinsic membrane-based vesicles that play a key role in both normal and pathological processes. Since their discovery, exosomes have been investigated as viable drug delivery systems and clinical indicators because of their magnitude and effectiveness in delivering biological components to targeted cells. Exosome characteristics are biocompatible, prefer tumor recruitment, have tunable targeting efficiency, and are stable, making them outstanding and eye-catching medication delivery systems for cancer and other disorders. There is great interest in using cell-released tiny vesicles that activate the immune system in the age of the fast development of cancer immunotherapy. Exosomes, which are cell-derived nanovesicles, have a lot of potential for application in cancer immunotherapy due to their immunogenicity and molecular transfer function. More significantly, exosomes can transfer their cargo to specified cells and so affect the phenotypic and immune-regulation capabilities of those cells. In this article, we summarize exosomes' biogenesis, isolation techniques, drug delivery, applications, and recent clinical updates. The use of exosomes as drug-delivery systems for small compounds, macromolecules, and nucleotides has recently advanced. We have tried to give holistic and exhaustive pieces of information showcasing current progress and clinical updates of exosomes.

In both developing and developed nations, pulmonary diseases are the major cause of mortality and disability. There has been a worldwide increase in the incidence of both acute and chronic respiratory illnesses, which poses a serious problem for the healthcare system. Lung cancer seems to be just one form of a parenchymal lung disorder, but there are many others, including chronic obstructive pulmonary disease (COPD), asthma, occupational lung diseases (asbestosis, pneumoconiosis), etc. Notably, chronic respiratory disorders cannot be cured, and acute abnormalities are notoriously difficult to treat. As a result, it is possible that therapeutic objectives could be achieved using nanotechnology in the form of either improved pharmacological efficacy or reduced toxicity. In addition, the incorporation of various nanostructures permits the enhancement of medication bioavailability, transport, and administration. Medicines and diagnostics based on nanotechnology have progressed significantly toward clinical application for the treatment of lung cancers. In recent years, scientists have shifted their focus towards exploring the potential of nanostructures in the treatment of other relevant respiratory illnesses. Micelles and polymeric nanoparticles are the two most studied nanostructures in a wide range of diseases. This study concludes with a summary of recent and pertinent research in drug delivery systems for the treatment of various pulmonary disorders, as well as trends, limitations, significance, and treatment and diagnostics employing nanotechnology, as well as future studies in this domain.

A recent study on the deployment of nanoparticles in the consumer and healthcare sectors has shown highly serious safety concerns. This is despite the fact that nanoparticles offer a vast array of applications and great promise. According to studies on how nanoparticles interact with neurons, the central nervous system experiences both negative and positive impacts central nervous system. With a maximum concentration of 0.1-1.0 wt.%, nanoparticles can be incorporated into materials to impart antibacterial and antiviral properties. Depending on the host or base materials utilised, this concentration may be transformed into a liquid phase release rate (leaching rate). For instance, nanoparticulate silver (Ag) or copper oxide (CuO)-filled epoxy resin exhibits extremely restricted release of the metal ions (Ag⁺ or Cu²⁺) into their surroundings unless they are physically removed or deteriorated. Nanoparticles are able to traverse a variety of barriers, including the blood-brain barrier (BBB) and skin, and are capable of penetrating biological systems and leaking into internal organs. In these circumstances, it is considered that the maximum drug toxicity test limit (10 g/ml), as measured in artificial cerebrospinal solution, is far lower than the concentration or dosage. As this is a fast-increasing industry, as the public exposure to these substances increases, so does their use. Thus, neurologists are inquisitive about how nanoparticles influence human neuronal cells in the central nervous system (CNS) in terms of both their potential benefits and drawbacks. This study will emphasise and address the significance of nanoparticles in human neuronal cells and how they affect the human brain and its activities

Introduction: In this study, arsenic nanoparticles containing folic acid (FA@As NPs) were synthesized by microwave irradiating a mixture of As2O3 and sodium borohydride solution in the presence of folic acid.

Methods: The physicochemical characteristics of the prepared NPs were studied by UV–visible spectroscopy, transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) analyses. Antioxidant activities, hemocompatibility, and cytotoxic effects of the prepared NPs were then evaluated. The attained results showed that the hexagonal FA@As NPs have a size range between 12.8 nm and 19.5 nm.

Results: The DPPH scavenging activity of FA@As NPs was found to be significantly greater than that of As NPs at concentrations ranging from 40 µg/mL to 2560 µg/mL (p<0.05). The hemolytic test confirmed that the measured hemolysis percentage (HP) for FA@As NPs and As NPs was 0% at concentrations between 20 to160 µg/mL, and for FA@As NPs, the measured HP was not significantly higher than As NPs at concentrations higher than 320 µg/mL (p>0.05).

Discussion: The necessary concentration for the death of half of the cells (IC50) for MDA-MB-231, MCF-7, and HUVEC cells treated (24 h) with FA@As NPs was measured to be 19.1±1.3 µg/mL, 15.4±1.1 µg/mL, and 16.8±1.2 µg/mL, respectively. However, further investigations are necessary to clarify the mechanisms behind the biological activities of FA@As NPs.

Aim: The present study aims to produce a novel therapeutic approach for the treatment of photoaging.

Background: Plant-derived exosome-like nanoparticles (PDENs) are nano-sized vesicles containing biomolecules released by multivesicular bodies. Recently, studies have shown the efficacy of exosomes in treating photoaging through increasing collagen synthesis and decreasing collagen degradation. In addition, some PDENs were also proven to contain bioactive metabolites, which also have potential antioxidant activity to mitigate the risk of photoaging.

Objective: Formulating and developing a gel and incorporating it with exosomes derived from golden cherry (Physalis minima).

Methods: The formulation was developed by first preparing various base formulations with different compositions and selecting the best through evaluation tests. The results showed that only polymer base natrosol with a concentration of 0.25% was suitable for incorporating exosomes. The selected base was then incorporated with various concentrations of golden cherry exosomes and was evaluated regarding its physical and stability profile.

Results: The result demonstrates that the incorporated gel displayed pleasant organoleptic properties and a pH compatible with the skin, with pseudoplastic flow and a suitable viscosity for topical application. The stability study also only revealed minor changes in viscosity and pH without affecting the general stability of the formulation. Formulation incorporating 0.25% golden cherry exosomes had shown the best stability profile compared to other concentrations. On characterization, although the incorporated exosomes showed heterogeneous particle size distribution (PI &amp;gt; 0.3), they still maintained their structural integrity. In addition, the incorporated exosomes showed antioxidant activity with IC50 of 372.435 μg/mL, which can help mitigate the risk of photoaging.

Conclusion: Golden cherry exosomes have been successfully incorporated into gel and, thus, can be potentially utilized as a novel therapeutic approach for the treatment of photoaging.

Background: Nanoparticles have received more and more attention in the vaccine and drug delivery systems field due to their specific properties. In particular, alginate and chitosan have been known as the most promising nano-carries. Digoxin-specific antibodies effectively manage acute and chronic digitalis poisoning using sheep antiserum.

Objectives: The present study aimed to develop alginate/chitosan nanoparticles as a carrier of Digoxin-KLH to promote the immune response by improving the hyper-immunization of animals.

Methods: The nanoparticles were produced by the ionic gelation method in mild conditions and the aqueous environment, which leads to the production of particles with favorable size, shape, high entrapment efficiency, and controlled release characteristics.

Results: The synthesized nanoparticles of 52 nm in diameter, 0.19 in PDI, and -33mv in zeta potential were considerably unparalleled and characterized by SEM, FTIR, and DSC. Nanoparticles resembled a spherical shell, smooth morphology, and homogeneous structure shown by SEM images. FTIR and DSC analyses confirmed conformational changes. Entrapment efficiency and loading capacity were 96% and 50%, respectively, via direct and indirect methods. The in vitro conjugate release profile, release kinetics, and mechanism of conjugate release from the nanoparticles were studied under simulated physiological conditions for various incubation periods. An initial burst effect revealed the release profile, followed by a continuous and controlled release phase. The compound release mechanism from the polymer was due to Fickian diffusion.

Conclusion: Our results indicated the prepared nanoparticles could be appropriate for the convenient delivery of the desired conjugate.

Background: Nebivolol HCl is a unique third-generation beta blocker that has less oral bioavailability and exhibits various adverse effects like gastrointestinal disturbance and abdominal pain.

Objectives: This study aimed to formulate and evaluate nebivolol HCl transferosomal transdermal patches to reduce the problems associated with oral delivery of the drug and enhancement of drug permeation through the skin.

Methods: Nebivolol HCl loaded transferosomes were prepared by thin film hydration method. Eight formulations were prepared based on the two independent variables, type of surfactant (Tween 80 and Span 80) and Phospholipid: Edge activator ratio and were evaluated for their vesicle size, PDI, and entrapment efficiency. The optimized formulations were incorporated into transdermal patches, which were evaluated for physicochemical properties, in-vitro and ex-vivo permeation, skin irritancy, and stability studies.

Results: The vesicle size of the transferosomes ranged from 49 nm to 93 nm, and EE% varied from 39% to 79%. Vesicles formed with Span 80 as an edge activator showed smaller vesicle size and greater EE% as compared to Tween 80. Based on the results, TW4 and SP4 were selected as the optimized formulations for further incorporation into the transdermal patches. In-vitro and ex-vivo permeation studies showed permeation in the order F2 > F3 > F1, indicating that transferosomal formulations showed superior permeation of the drug compared to plain Nebivolol HCl patches. Span 80 transferosomes showed a slightly better permeation than Tween 80. Stability studies showed that transferosomes and the transdermal patches demonstrated good stability under proper storage conditions.

Conclusion: The study concluded that transferosomal patches of Nebivolol HCl could be used as a potential approach with effective transdermal delivery for the management of hypertension.

Background: Mahkota Dewa (Phaleria macrocarpa) seed has various phytochemical compounds and low pharmacological activities, including antioxidant and anti-inflammatory activities.

Objective: This research aimed to study nanoemulsion preparations of Mahkota Dewa seed (NE-BMD) for their anti-oxidant and anti-inflammatory properties.

Methods: The nanoemulsion was prepared using an ultrasonication probe and followed by selecting two formulations, F7 and F8. The anti-oxidant activity test was carried out using the DPPH method, meanwhile, the anti-inflammatory activity test was conducted using the protein denaturation method with Bovine Serum Albumin (BSA) for in vitro studies. In addition, for in vivo studies, the plethysmometer method was used with 1% carrageenan as an inducer.

Results: The characterization of NE-BMD preparations showed that the particle size and polydispersity index were 26,83 ± 1,27 nm (PI: 0.36 ± 0.03) and 30.73 ± 1.50 nm (PI: 0.32 ± 0.06) for NE-BMD F7 and F8 formulation, respectively. In addition, the anti-oxidant activity test revealed that the IC50 values of NE_BMD F7 and F8 were 15.62 ± 1.40 µg/ml and 28.39 ± 4.69 µg/ml, respectively. The protein denaturation test showed that the IC50 values for NE-BMD F7 and F8 were 94.39 ± 1.24 µg/ml and 196.63 ± 1.61 µg/ml, respectively. Meanwhile, the study of anti-inflammatory in vivo for NE-BMD F7 with a 1 g/kg BW dose showed a significant improvement in anti-inflammatory activity compared to BMD extract.

Conclusion: This research suggests that due to the smaller drug particle size, the nanoemulsion dosage form of Mahkota Dewa seed extract has anti-oxidant and anti-inflammatory activities, thus emerging as an adjunct alternative treatment for inflammation.