Current Drug Delivery - Current Issue

Exosomes are unique bio-nanomaterials possessing significant value and potential for drug delivery systems. However, to date, no bibliometric studies in this field have been reported. Our aim is to explore the research hotspots and trends of exosome drug-carrying systems across various medical fields through bibliometric analyses.

Articles and reviews related to “exosome” and “drug delivery” are retrieved from the Web of Science Core Collection. VOSviewer, CiteSpace, Scimago Graphica, and Origin 2021 are employed for bibliometric analyses.

A total of 771 articles from 60 countries, such as China and the United States, are included. The number of papers concerning exosomal drug delivery systems has been increasing yearly. The main research institutions are the Chinese Academy of Sciences, Shanghai Jiao Tong University, Huazhong University of Science and Technology, Fudan University, and Sichuan University. The Journal of Controlled Release is the most prevalent and frequently cited journal in this field. These papers are authored by 247 individuals, with Ando, Hidenori having the highest number of publications and Alvarez-Erviti L receiving the most citations. “Extracellular vesicles”, “drug delivery”, “in vitro”, “nanoparticles”, “cells”, “delivery”, and “mesenchymal stem cells” are the principal keywords for this hotspot.

This pioneering bibliometric study offers a comprehensive overview of the research trends and advancements in exosomal drug delivery systems in medicine over the past fifteen years.

Assessing the cytotoxicity of gold nanoparticles (GNPs) has gained importance due to their development in the biomedical field.

In this study, we systematically synthesized gold nanorods (GNRs), gold nanobipyramids (GNBPs), and gold nanocups (GNCs) using a seed-mediated method, with an average length of 32.53 ± 4.67 nm, 72.90 ± 7.54 nm and 118.01 ± 11.02 nm, respectively.

Furthermore, using the cell counting kit-8 (CCK-8) assay, we assessed the cellular cytotoxicity of three different types of GNPs with various different surface coatings, such as organic cetyltrimethylammonium bromide (CTAB) and polyethylene glycol (PEG). The results showed that the cytotoxic behavior of GNPs was shape-dependent in the concentration range of 3.125 -100 μg/mL. The types of GNPs and their surface coating had a significant impact on how the GNPs behaved in cells. Compared to PEG-coated GNPs, which do not induce cell injury, CTAB-coated GNPs show more noticeable cytotoxicity.

Furthermore, compared to GNCs, the toxicity of GNRs and GNBPs against GES-1 cells, RAW 264.7 cells and LX-2 cells was greater. Our research provides an important new understanding of the effects of surface modification on the biocompatibility and the shape of GNPs in the biomedical field.

Poly(methyl vinyl ether co-maleic acid) (PMVE/MA) hydrogel microneedles (HMN) are investigated for transdermal delivery of macromolecular drugs owing to their biocompatibility and super-swelling properties. However, the drug delivery efficacy reduces with increasing molecular weight due to the entrapment within the HMN matrices. Furthermore, integrating external drug reservoirs extends the drug diffusion path and reduces the efficiency of drug permeation.

A direct drug loading approach in the HMN matrix was introduced in this work following a pH modification step. The effect of pH modification on the physicochemical properties of HMN was studied. Then, bovine serum albumin (BSA), a model protein, was loaded into the pH-modified HMN, and the morphological changes in HMN and protein stability were also assessed. Finally, the efficacy of BSA-loaded HMN in the transdermal delivery was evaluated ex vivo.

A significant increase in swelling was recorded following the pH modification of HMN (p < 0.001). The structure of pH-modified hydrogel was highly porous, and ATR-FTIR spectra indicated a shift in the carboxylic peak. The secondary structure of BSA loaded in the pH-modified HMN was also preserved. The BSA-loaded HMN mediated a sustained ex-vivo drug release with a cumulative release of 64.70% (3.88 mg) in 24 h.

The model drug-incorporated PMVE/MA HMN system shows potential for sustainable transdermal delivery of proteins.

Overcoming the poor aqueous solubility of small-molecule drugs is a major challenge in developing clinical pharmaceuticals. Felodipine (FLDP), an L-type calcium calcium channel blocker, is a poorly water-soluble drug.

The study aimed to explore the potential applications of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (Soluplus) stabilized amorphous dispersions for augmenting the oral delivery of poorly water-soluble drugs.

Soluplus-stabilized amorphous FLDP (FLDP-SSAs) was prepared using a two-phase mixing method. The samples were analyzed for their microscopic and macroscopic behavior using polarized light microscopy (PLM), differential scanning calorimetry (DSC), molecular simulation, and in vitro dissolution studies. Subsequently, the pharmacokinetics of FLDP-SSAs were evaluated.

The maximum drug-to-Soluplus mass ratio of FLDP-SSAs was 50:50, with a drug concentration of 8.0 mg/mL. They exhibited an amorphous nature, as confirmed by PLM and DSC. FLDP-SSAs generated nanoparticles with a particle size of approximately 50 nm during in vitro dissolution. Compared to FLDP oral solution, FLDP-SSAs exhibited higher solubility due to their amorphous nature and the generation of nanoparticles. The area under the curve (AUC) for oral FLDP-SSAs was 16.7-fold larger than that of the FLDP suspension.

FLDP-SSAs could stabilize FLDP in an amorphous state and serve as drug carriers to enhance oral absorption.

Superparamagnetic iron oxide nanoparticles (SPIONs) with a specific size range of 15-70 nm are usually considered nontoxic substances with superior antibacterial activity, making them strong candidates for wound dressing applications. Although SPIONs have significant antibacterial activity, their ability to treat infected wounds still needs to be explored.

The objective of the present study was to synthesize antibacterial SPIONs (G-SPIONs) using aqueous garlic extract as a bioreducing agent and evaluate the synthesized G-SPIONs-incorporated nanohydrogel for wound healing potential.

Synthesized G-SPIONs were characterized by SEM, zeta potential, VSM, FTIR, etc. The antibacterial effects of G-SPIONs were evaluated against S. epidermidis, S. aureus, and E. coli, as compared to garlic extract. The synthesized G-SPIONs were further incorporated into the chitosan-based hydrogel (ChiG-SPIONs) to assess their wound healing potential using the in vivo rat model.

The synthesized G-SPIONs had a positive surface charge of +3.82 mV and were spherical, with sizes ranging between 20-80 nm. Additionally, their hemo-biocompatible nature was confirmed by hemolysis assay. The magnetic nature of synthesized G-SPIONs was investigated using a vibrating sample magnetometer, and the saturation magnetization (Ms) was found to be 53.793emu/g. The in vivo wound healing study involving rats revealed a wound contraction rate of around 95% with improved skin regeneration. The histopathological examination demonstrated a faster rate of re-epithelialization with regeneration of blood vessels and hair follicles.

The results demonstrated that the developed ChiG-SPIONs could be a novel and efficient nanohydrogel dressing material for the effective management of wound infections.

Type 2 diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia. Natural compounds derived from plants, such as Ipomoea batatas, have shown therapeutic potential for its treatment.

A starch-based biopolymer was developed and functionalized with a methanolic extract of Ipomoea batatas (IBM). Its physicochemical properties, such as swelling capacity, encapsulation efficiency, and extract release, were evaluated. In vivo tests were conducted on diabetic Danio rerio using two administration routes: immersion and oral delivery.

The biopolymer exhibited a swelling capacity of 333.03% and an encapsulation efficiency of 47.78%. In the zebrafish model, significant reductions in glucose, triglycerides, and cholesterol levels were observed, along with inhibition of advanced glycation end products (AGEs) formation in groups treated with IBM and BP-IBM.

The results suggest that the biopolymer preserves the chemical integrity of the extract and improves its bioavailability, enabling a significant therapeutic effect. The dual administration routes provide flexibility and demonstrate the efficacy of the delivery system.

The starch-based system functionalized with I. batatas extract proved to be a promising and non-toxic platform for the delivery of bioactive metabolites in type 2 diabetes models, with potential for future therapeutic applications.