In many clinical applications, the transdermal route is used as an alternative approach to avoid the significant limitations associated with oral drug delivery. There is a long history for drug delivery through the skin utilizing transdermal microneedle arrays. Microneedles are reported to be versatile and very efficient devices. This technique has spurred both industrial and scientific curiosity, due to its outstanding characteristics such as painless penetration, affordability, excellent medicinal efficiency, and relative protection. Microneedles possess outstanding properties for diverse biomedical uses such as the delivery of very large substances with ionic and hydrophilic physicochemical properties. Importantly, microneedles are applicable in numerous biomedical fields such as therapy, diagnosis, and vaccine administration. Microneedles are emerging tools that have shown profound potential for biomedical applications. Transdermal microneedle technologies are likely to become a preferred route of therapeutic substances administration in the future since they are effective, painless, and affordable. In this review, we summarize recent advances in microneedles for therapeutic applications. We explore their constituent materials and fabrication methods that improve the delivery of critical therapeutic substances through the skin. We further discuss the practicality of advanced microneedles used as drug delivery tools.
The Warburg Effect has emerged as a potential drug target because, in some cancer cell lines, it is sufficient to subvert it in order to kill cancer cells. It has also been shown that the Warburg Effect occurs in innate immune cells upon infection. Innate immune cells play critical roles in the tumour microenvironment but the Warburg Effect is not fully understood in monocytes. Furthermore, it is important to understand the impact of infections on key players in the tumour microenvironment because inflammatory conditions often precede carcinogenesis and mutated oncogenes induce inflammation. We investigated the metabolic programme in the acute monocytic leukaemia cell line, THP-1 in the presence and absence of lipopolysaccharide, mimicking bacterial infections. We found that stimulation of THP-1 cells by LPS induces a subset of pro-inflammatory chemokines and enhances the Warburg Effect. Surprisingly, perturbation of the Warburg Effect in these cells does not lead to cell death in contrast to what was observed in non-myeloid cancer cell lines in a previous study. These findings indicate that the Warburg Effect and inflammation are activated by bacterial lipopolysaccharide and may have a profound influence on the microenvironment.
Traumatic brain injuries (TBIs) are still a challenge for the field of modern medicine. Many treatment options such as autologous grafts and stem cells show limited promise for the treatment and the reversibility of damage caused by TBIs. Injury beyond the critical size necessitates the implementation of scaffolds that function as surrogate extracellular matrices. Two scaffolds were synthesised utilising polysaccharides, chitosan and hyaluronic acid in conjunction with gelatin. Both scaffolds were chemically crosslinked using a naturally derived crosslinker, Genipin. The polysaccharides increased the mechanical strength of each scaffold, while gelatin provided the bioactive sequence, which promoted cellular interactions. The effect of crosslinking was investigated, and the crosslinked hydrogels showed higher thermal decomposition temperatures, increased resistance to degradation, and pore sizes ranging from 72.789 ± 16.85 µm for the full interpenetrating polymer networks (IPNs) and 84.289 ± 7.658 μm for the semi-IPN. The scaffolds were loaded with Dexamethasone-21-phosphate to investigate their efficacy as a drug delivery vehicle, and the full IPN showed a 100% release in 10 days, while the semi-IPN showed a burst release in 6 h. Both scaffolds stimulated the proliferation of rat pheochromocytoma (PC12) and human glioblastoma multiforme (A172) cell cultures and also provided signals for A172 cell migration. Both scaffolds can be used as potential drug delivery vehicles and as artificial extracellular matrices for potential neural regeneration.
Nanotechnology has aided in the advancement of drug delivery for the treatment of several neurological disorders including depression. Depression is a relatively common mental disorder which is characterized by a severe imbalance of neurotransmitters. Several current therapeutic regimens against depression display drawbacks which include low bioavailability, delayed therapeutic outcome, undesirable side effects and drug toxicity due to high doses. The blood–brain barrier limits the entry of the drugs into the brain matrix, resulting in low bioavailability and tissue damage due to drug accumulation. Due to their size and physico-chemical properties, nanotechnological drug delivery systems present a promising strategy to enhance the delivery of nanomedicines into the brain matrix, thereby improving bioavailability and limiting toxicity. Furthermore, ligand-complexed nanocarriers can improve drug specificity and antidepressant efficacy and reduce drug toxicity. Biopolymers and nanocarriers can also be employed to enhance controlled drug release and reduce the hepatic first-pass effect, hence reducing the dosing frequency. This manuscript reviews recent advances in different biopolymers, such as polysaccharides and other nanocarriers, for targeted antidepressant drug delivery to the brain. It probes nano-based strategies that can be employed to enhance the therapeutic efficacy of antidepressants through the oral, intranasal, and parenteral routes of administration.
22 July 2024 in Journal of Biomaterials Science, Polymer Edition
Burn wounds are associated with infections, drug resistance, allergic reactions, odour, bleeding, excess exudates, and scars, requiring prolonged hospital stay. It is crucial to develop wound dressings that can effectively combat allergic reactions and drug resistance, inhibit infections, and absorb excess exudates to accelerate wound healing. To overcome the above-mentioned problems associated with burn wounds, SA/PVA/PLGA/Capparis sepiaria and SA/PVA/Capparis sepiaria nanofibers incorporated with Capparis sepiaria plant extract were prepared using an electrospinning technique. Fourier-transform infrared spectroscopy confirmed the successful incorporation of the extract into the nanofibers without any interaction between the extract and the polymers. The nanofibers displayed porous morphology and a rough surface suitable for cellular adhesion and proliferation. SA/PVA/PLGA/Capparis sepiaria and SA/PVA/Capparis sepiaria nanofibers demonstrated significant antibacterial effects against wound infection-associated bacterial strains: Pseudomonas aeruginosa, Enterococcus faecalis, Mycobaterium smegmatis, Escherichia coli, Enterobacter cloacae, Proteus vulgaris, and Staphylococcus aureus. Cytocompatibility studies using HaCaT cells revealed the non-toxicity of the nanofibers. SA/PVA/PLGA/Capparis sepiaria and SA/PVA/Capparis sepiaria nanofibers exhibited hemostatic properties, resulting from the synergistic effect of the plant extract and polymers. The in vitro scratch wound healing assay showed that the SA/PVA/Capparis sepiaria nanofiber wound-healing capability is more than the plant extract and a commercially available wound dressing. The wound-healing potential of SA/PVA/Capparis sepiaria nanofiber is attributed to the synergistic effect of the phytochemicals present in the extract, their porosity, and the ECM-mimicking structure of the nanofibers. The findings suggest that the electrospun nanofibers loaded with Capparis sepiaria extract are promising wound dressings that should be explored for burn wounds.
The application of Superparamagnetic Iron Oxide Nanoparticles (SPIONs) as a nanomedicine for Non-Small Cell Lung Carcinoma (NSCLC) can provide effective delivery of anticancer drugs with minimal side-effects. SPIONs have the flexibility to be modified to achieve enhanced oading of hydrophobic anticancer drugs such as paclitaxel (PTX). The purpose of this study was to synthesize novel trans-10, cis-12 conjugated linoleic acid (CLA)-coated SPIONs loaded with PTX to enhance the anti-proliferative activity of PTX. CLA-coated PTX-SPIONs with a particle size and zeta potential of 96.5 ± 0.6 nm and −27.3 ± 1.9 mV, respectively, were synthesized. The superparamagnetism of the CLA-coated PTX-SPIONs was confirmed, with saturation magnetization of 60 emu/g and 29 Oe coercivity. CLA-coated PTX-SPIONs had a drug loading efficiency of 98.5% and demonstrated sustained site-specific in vitro release of PTX over 24 h (i.e., 94% at pH 6.8 mimicking the tumor microenvironment). Enhanced anti-proliferative activity was also observed with the CLA-coated PTX-SPIONs against a lung adenocarcinoma (A549) cell line after 72 h, with a recorded cell viability of 17.1%. The CLA-coated PTX-SPIONs demonstrated enhanced suppression of A549 cell proliferation compared to pristine PTX, thus suggesting potential application of the nanomedicine as an effective site-specific delivery system for enhanced therapeutic activity in NSCLC therapy.