Drug Delivery Research Articles

Current Expansion of Silver and Gold Nanomaterials towards Cancer Theranostics: Development of Therapeutics

Abstract: Nanomaterial-based therapeutics is an emerging tool for the treatment of numerous types of cancer. Various types of polymeric, lipid and inorganic nanoparticles (NPs) result in a wider series of applications in cancer diagnosis and therapeutics. The NPs properties are due to high surface area to volume ratio, surface plasmon resonance, absorption in the visible spectrum and light scattering. These unique characteristics of NPs arise due to their optical surface properties for conjugation/surface modification and smaller size. In cancer therapeutics, NPs based products are used as a biomarker for early detection/diagnosis of tumours, drug nano-conjugates for the delivery of chemotherapeutic drugs to the tumour-specific site, chemo-protective agents, etc. : Furthermore, other advantages of NPs are biocompatibility, lesser toxicity, enhanced permeability and retention effect, higher stability, and specific targeting with a selective accumulation of nano drugs in the tissue of the tumour. The selective targeting of NPs to tumour tissue is possible by adding surface-active targeting agents i.e., antibodies. The selective transport of drug NPs conjugates to the cancer cells is increased and extravagated due to permeable vasculature from endothelial cells gap while failing the transport of drug NPs conjugates in normal cells. This review emphasizes metallic NPs, including silver NPs (AgNPs) and gold NPs (AuNPs), which are extensively reconnoitered in various applications in cellular targeting, imaging, drug delivery, DNA-NPs conjugates for biosensor/point of care devices development, photothermal/photodynamic therapy, protein-protein interaction, etc. In addition, this review discussed different synthetic methods of AgNPs and AuNPs and characterization methods. Furthermore, it highlighted the different properties and applications of AgNPs and AuNPs in cancer theranostics.

A chiral metal–organic polyhedron used as stationary phase for gas chromatographic separations

Metal-organic polyhedra (MOPs), as a novel class of porous materials, exhibit distinctive application potential in molecular recognition, separation, catalysis, luminescent materials, drug delivery, and biomedicine owing to their tunable geometric shape and size, well-defined cavities, and discrete characteristics. In this study, we report that a chiral MOP [Cu12(LV)12(H2O)12] (V = L-valine) coated capillary column was used for gas chromatographic separations. The MOP coated capillary column offered the efficient separation of n-alkanes, alkylbenzenes, n-alcohols, multiple types of isomers, and enantiomers with high selectivity. Various enantiomers including esters, halogenated hydrocarbons, alcohols, ethers, aldehydes, and amino acid derivatives were well resolved on this chiral column, especially for some amino acid derivatives (e.g., Rs = 5.24 for tyrosine derivative). Compared with the commercial β-DEX 120 column for separation of the tested racemates, the chiral resolution performance of the MOP coated column can be complementary to that of β-DEX 120 column. Using 1,2-dichloropropane and o, m, p-dichlorobenzene as analytes, the MOP coated column exhibited good stability and reproducibility for gas chromatographic separations. The relative standard deviations (RSDs) of the retention time and peak area for repeated separation of 1, 2-dichloropropane and o, m, p-dichlorobenzene were less than 1.15 and 0.79 %, respectively. The results show that the chiral MOP holds great potential as a novel type of CSP for application in gas chromatography.

Novel Approaches for the Management of Type 2 Diabetes Mellitus: An Update.

Diabetes mellitus is an irreversible, chronic metabolic disorder indicated by hyperglycemia. It is now considered a worldwide pandemic. T2DM, a spectrum of diseases initially caused by tissue insulin resistance and slowly developing to a state characterized by absolute loss of secretory action of the β cells of the pancreas, is thought to be caused by reduced insulin secretion, resistance to tissue activities of insulin, or a combination of both. Insulin secretagogues, biguanides, insulin sensitizers, alpha-glucosidase inhibitors, incretin mimetics, amylin antagonists, and sodium-glucose co-transporter-2 (SGLT2) inhibitors are the main medications used to treat T2DM. Several of these medication's traditional dosage forms have some disadvantages, including frequent dosing, a brief half-life, and limited absorption. Hence, attempts have been made to develop new drug delivery systems for oral antidiabetics to ameliorate the difficulties associated with conventional dosage forms. In comparison to traditional treatments, this review examines the utilization of various innovative therapies (such as microparticles, nanoparticles, liposomes, niosomes, phytosomes, and transdermal drug delivery systems) to improve the distribution of various oral hypoglycemic medications. In this review, we have also discussed some new promising candidates that have been approved recently by the US Food and Drug Administration for the treatment of T2DM, like semaglutide, tirzepatide, and ertugliflozin. They are used as a single therapy and also as combination therapy with drugs like metformin and sitagliptin.

From Traditional Medicine to Advanced Therapeutics: The Renaissance of Phyto-nano Interventions in Psoriasis.

Psoriasis is an autoimmune systemic chronic inflammatory disease that exhibits characteristic detrimental effects on the skin, often leading to infections or comorbid conditions. The multifaceted nature of psoriasis has made it very challenging to treat, especially with current chemotherapy options. Therefore, it is essential to consider phytoconstituents as novel alternatives. However, despite demonstrating higher anti-inflammatory, anti-psoriasis, and immunomodulatory potential, their clinical usage is hindered due to their poor physicochemical properties. To address these drawbacks, nanoparticulate drug delivery systems have been developed, helping to achieve better permeation of phytoconstituents through topical administration. This has breathed new life into traditional systems of medicine, particularly in the context of treating psoriasis. In this current review, we present a detailed, comprehensive, and up-to-date analysis of the literature, which will contribute to affirming the clinical role of phyto-nano interventions against psoriasis.

Preparation of Ketoconazole-loaded Nanoemulsions for Ophthalmic Delivery: Characterization and In-vitro Antifungal Activity Evaluation

Background: Nanoemulsions (N.E.s) capable of ocular bioavailability elevation can be used for poor water-soluble drugs such as ketoconazole (K.Z.). The current investigation was designed for the purpose of overcoming this issue by developing K.Z. containing N.E.s for ophthalmic drug delivery with appropriate therapeutic efficiency. Methods: The preparation of ketoconazole N.E.s was performed by the low-energy technique. According to the phase diagram, three stable formulations were selected for more physicochemical analyses, including particle size, polydispersity index, pH, refractive index and viscosity. Finally, drug release patterns and in-vitro antifungal activity were assessed for the final selected formulation. Results: The developed N.E. formulations with droplet sizes less than 20 nm showed appropriate physicochemical characteristics for ocular delivery. The selected formulation released 100% of the encapsulated drug during 24 h. Moreover, antifungal assessments showed that prepared N.E. had acceptable in-vitro antifungal activity. Conclusions: Based on our findings, it can be concluded that N.E.s could be applied as effective carriers for the ophthalmic delivery of ketoconazole.

Efficacy of Y-90 TARE in advanced HCC: an experience with hybrid Angio-CT and glass microspheres

BackgroundHepatocellular carcinoma is one of the most common malignancies worldwide. Transarterial radioembolization (TARE) involves selective intra-arterial administration of microspheres loaded with a radioactive compound like Yttrium90. Conventionally, C-arm based cone-beam computed tomography has been used extensively during TARE. However, Angio-CT is a relatively new modality which combines the advantages of both fluoroscopy and Computed Tomography (CT). There is scarce literature detailing the use of Angio-CT in Y90 TARE. MethodsThis was a retrospective study of primary liver cancer cases in which TARE procedure was done from November 2017 to December 2021. Glass-based Y-90 microspheres were used in all these cases. All the cases were performed in the hybrid Angio-CT suite. A Single Photon Emission Computed Tomography – Computed Tomography (SPECT-CT) done post planning session determined the lung shunt fraction and confirmed the accurate targeting of the lesion. Post drug delivery, PET-CT was obtained to confirm the distribution of the Y-90 particles. The technical success, median follow-up, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were recorded. ResultsA total of 56 hepatocellular carcinoma patients underwent TARE during this period out of which 36 patients (30 males and 6 females) underwent Y90 TARE. The etiology of cirrhosis included non-alcoholic steatohepatitis (NASH) (11), hepatitis C (HCV) (11), hepatitis B (HBV) (9), metabolic dysfunction and alcohol associated liver disease (MetALD) (2), alcoholic liver disease (ALD) (1), cryptogenic (1) and autoimmune hepatitis (AIH) (1). The technical success was 100% and median follow-up was 7 months (range: 1 - 32 months). The median OS was 15 months (range 10.73 – 19.27 months; 95% CI) and the median local PFS was 4 months (range 3.03 – 4.97 months; 95% CI). The ORR (best response, CR + PR) was 58%. No major complications were seen in this study. ConclusionTARE is a viable option for liver cancers in all stages but more so in the advanced stages. The use of Angio-CT in TARE aids in the precise delivery of the particles to the tumour and avoids non-target embolization.

Tumor Targeting with Apatinib-loaded Nanoparticles and Sonodynamic Combined Therapy

This study implies the enhancement of apatinib killing effect in 4T1 tumor cells through constructing drug-loaded nanoparticles apatinib/Ce6@ZIF-8@Membranes (aCZM) to enhance tumor therapeutic targeting and reduce toxic side following sonodynamic therapy (SDT). apatinib/Ce6@ZIF-8 (aCZ) were synthesized by in situ encapsulation, and aCZM were constructed by encapsulating the nanoparticles with extracted breast cancer 4T1 cell membranes. aCZM were characterized and tested for the stability by electron microscopy, and the membrane proteins on the nanoparticles' surface were assessed using SDS-PAGE gel electrophoresis. The cell viability of 4T1 cells following treatment with aCZM was tested using cell counting kit-8 (CCK-8). The uptake of nanoparticles was detected by laser confocal microscopy and flow cytometry, and the SDT-mediated production of reactive oxygen species (ROS) was verified by singlet oxygen sensor green (SOSG), electron spin resonance (ESR), and DCFH-DA fluorescent probes. The CCK-8 assay and flow cytometry using Calcein/PI were used to assess the antitumoral effect of aCZM nanoparticles under SDT. The biosafety of aCZM was further verified in vitro and in vivo using the hemolysis assay, routine blood test and H&E staining of vital organs in Balb/c mice. aCZM with an average particle size of about 210.26 nm were successfully synthesized. The results of the SDS-PAGE gel electrophoresis experiment showed that aCZM have a band similar to that of pure cell membrane proteins. The CCK-8 assay demonstrated the absence of effects on cell viability at a low concentration range, and the relative cell survival rate reached more than 95%. Laser confocal microscopy and flow cytometry analysis showed that aCZM treated group has the strongest fluorescence and the highest cellular uptake of nanoparticles. SOSG, ESR, and DCFH-DA fluorescent probes all indicated that the aCZM + SDT treated group has the highest ROS production. The CCK-8 assay also showed that when the ultrasound intensity was fixed at 0.5 W/cm2, the relative cell survival rates in the medium concentration group (10 μg/ml) (5.54 ± 1.26%) and the high concentration group (20 μg/ml) (2.14 ± 1.63%) were significantly lower than those in the low concentration group (5 μg/ml) (53.40 ± 4.25%). Moreover, there was a concentration and intensity dependence associated with the cell-killing effect. The mortality rate of the aCZM in the ultrasound group (44.95±3.03%) was significantly higher than that of the non-ultrasound (17.00±2.26%) group and aCZ + SDT group (24.85 ± 3.08%) (P<0.0001). The live and dead cells' staining (Calcein/PI) also supported this result. Finally, in vitro hemolysis test at 4 and 24 hours showed that the hemolysis rate of the highest concentration group was less than 1%. The blood routine, biochemistry, and H&E staining results of major organs in Balb/c mice undergoing nano-treatments showed no obvious functional abnormalities and tissue damage in 30 days. In this study, a multifunctional bionic drug delivery nanoparticles (aCZM) system with good biosafety and compatibility in response to acoustic dynamics was successfully constructed and characterized. This system enhanced apatinib killing effect on tumor cells and reduced toxic side effects under SDT.

Fast dissolving tablet

Fast dissolving tablets have emerged as a popular dosage form, particularly beneficial for pediatric and geriatric patients facing challenges such as dysphagia or hand tremors. These tablets dissolve quickly in saliva without needing water, enhancing compliance and effectiveness of therapy. They offer advantages like easy portability, accurate dosing, and improved bioavailability. Various technologies, including spray drying and melt granulation, have been developed for their manufacturing. This review provides comprehensive information on fast dissolving tablets, covering their definition, advantages, limitations, challenges, and available formulations. The design of an oral drug delivery system prioritizes convenience in administration and improved patient compliance, making it the preferred route of drug delivery despite certain drawbacks. Over the last decade, there has been a growing demand for Fast Disintegrating Tablets (FDTS), turning this field into a rapidly expanding area within the pharmaceutical industry. The formulation’s popularity and effectiveness have led to the development of various FDT technologies. These technologies aim to achieve rapid tablet disintegration and mouth dissolution within five seconds, eliminating the need for chewing or water intake. This characteristic is particularly advantageous for populations such as pediatrics, geriatrics, and patients facing difficulties in swallowing conventional tablets and capsules. The formulation of an easily administrable dosage form, considering challenges like swallowing difficulties and low patient compliance, has driven the creation of orally disintegrating tablets. Traditional preparation methods include spray drying, freeze drying, direct compression, molding, and sublimation. In addition, new technologies have been devised to enhance the production of orodispersible tablets.

Formulation and validation on UV spectroscopy of Herbosomes loaded Mahonia aquifolium cream for psoriasis

Herbosome technology enhances the bioavailability of herbal excerpts. Herbosome act as the ground between the new delivery system and conventional delivery system. It's a complex fashion applied to phytopharmaceuticals for the improvement of bioavailability of herbal excerpt for medicinal operations. This composition overviews about herbosome technology, recent advance, their operation for colorful standardized herbal excerpts and aims to give complete of natural active constituents and phospholipid (phosphatidylcholine, phosphatidylserine etc.) which increases immersion of herbal excerpt. Herbosome is the new arising scientific information, characterization about herbosomes as a promising drug delivery system. Psoriasis is an inflammatory skin condition characterized by scaling with inflammation (pain, edema, warmth, and redness) that results in regions of thick, red skin covered in silvery scales. These spots can be itchy or painful. Systemic treatment, topical therapy, and phototherapy are all now used to treat psoriasis. These treatments have a variety of negative and perhaps fatal side effects. Patients with psoriasis are more likely to acquire other conditions such as psoriatic arthritis, anxiety and depression, cancer, metabolic syndrome, cardiovascular disease, and Crohn's disease. The majority of people use herbal medicine because it is readily available, inexpensive, and effective. Many plants have promising features, including significant results in the treatment of psoriasis. The present study plans to emphasize such plants, herbal formulations, and associated therapy, which could add value to the development of a better, safe, and efficacious formulation to treat psoriasis that may help new researchers in this field

Transfer of ANS-Like Drugs from Micellar Drug Delivery Systems to Albumin Is Highly Favorable and Protected from Competition with Surfactant by "Reserved" Binding Sites.

Micellar drug delivery systems (MDDS) for the intravenous administration of poorly soluble drugs have great advantages over alternative formulations in terms of the safety of their excipients, storage stability, and straightforward production. A classic example is mixed micelles of glycocholate (GC) and lecithin, both endogenous substances in human blood. What limits the use of MDDS is the complexity of the transitions after injection. In particular, as the MDDS disintegrate partially or completely after injection, the drug has to be transferred safely to endogenous carriers in the blood, such as human serum albumin (HSA). If this transfer is compromised, the drug might precipitate─a process that needs to be excluded under all circumstances. The key question of this paper is whether the high local concentration of GC at the moment and site of MDDS dissolution might transiently saturate HSA binding sites and, hence, endanger quick drug transfer. To address this question, we have used a new approach, which is time-resolved fluorescence spectroscopy of the single tryptophan in HSA, Trp-214, to characterize the competitive binding of GC and the drug substitute anilinonaphthalenesulfonate (ANS) to HSA. Time-resolved fluorescence of Trp-214 showed important advantages over established methods for tackling this problem. ANS has been the standard "model drug" to study albumin binding for decades, given its structural similarity to the class of naphthalene-containing acidic drugs and the fact that it is displaced from HSA by numerous drugs (which presumably bind to the same sites). Our complex global fit uses the critical approximation that the average lifetimes behave similarly to a single lifetime, but the resulting errors are found to be moderate and the results provide a convincing explanation of the, at first glance, counterintuitive behavior. Accordingly, and largely in line with the literature, we observed two types of sites binding ANS at HSA: 3 type A, rather peripheral, and 2 type B, likely more central sites. The latter quench Trp-214 by Förster Resonance Energy Transfer (FRET) with a rate constant of ≈0.4 ns-1 per ANS. Adding millimolar concentrations of GC displaces ANS from the A sites but not from B sites. At incomplete ANS saturation, this causes a GC-induced translocation of ANS from A to the more FRET-active B sites. This leads to the apparent paradox that the partial displacement of ANS from HSA increases its quenching effect on Trp-214. The most important conclusion is that (ANS-like) drugs cannot be displaced from the type-B sites, and consequently, drug transfer to these sites is not impaired by competitive binding of GC in the vicinity of a dissolving micelle. The second conclusion is that for unbound GC above the CMC (9 mM), ANS equilibrates between HSA and GC micelles but with a strong preference for free sites on HSA. That means that even persisting micelles would lose their cargo readily once exposed to HSA. For all MDDS sharing this property, targeted drug delivery approaches involving them as the nanocarrier would be pointless.

Self-Assembled Recombinant Elastin and Globular Protein Vesicles with Tunable Properties for Diverse Applications.

ConspectusVesicles are self-assembled structures comprised of a membrane-like exterior surrounding a hollow lumen with applications in drug delivery, artificial cells, and micro-bioreactors. Lipid or polymer vesicles are the most common and are made of lipids or polymers, respectively. They are highly useful structures for many applications but it can be challenging to decorate them with proteins or encapsulate proteins in them, owing to the use of organic solvent in their formation and the large size of proteins relative to lipid or polymer molecules. By utilization of recombinant fusion proteins to make vesicles, specific protein domains can be directly incorporated while also imparting tunability and stability. Protein vesicle assembly relies on the design and use of self-assembling amphiphilic proteins. A specific protein vesicle platform made in purely aqueous conditions of a globular, functional protein fused to a glutamate-rich leucine zipper (ZE) and a thermoresponsive elastin-like polypeptide (ELP) fused to an arginine-rich leucine zipper (ZR) is discussed here. The hydrophobic conformational change of the ELP above its transition temperature drives assembly, and strong ZE/ZR binding enables incorporation of the desired functional protein. Mixing the soluble proteins on ice induces zipper binding, and then warming above the ELP transition temperature (Tt) triggers the transition to and growth of protein-rich coacervates and, finally, reorganization of proteins into vesicles. Vesicle size is tunable based on salt concentration, rate of heating, protein concentration, size of the globular protein, molar ratio of the proteins, and the ELP sequence. Increasing the salt concentration decreases vesicle size by decreasing the Tt, resulting in a shorter coacervation transition stage. Likewise, directly changing the heating rate also changes this time and increasing protein concentration increases coalescence. Increasing globular protein size decreases the size of the vesicle due to steric hindrance. By changing the ELP sequence, which consists of (VPGXG)n, through the guest residue (X) or number of repeats (n), Tt is changed, affecting size. Additionally, the chemical nature of X variation has endowed vesicles with stimuli responsiveness and stability at physiological conditions.Protein vesicles have been used for biocatalysis, biomacromolecular drug delivery, and vaccine applications. Photo-cross-linkable vesicles were used to deliver small molecule cargo to cancer cells in vitro and antigen to immune cells in vivo. pH-responsive vesicles effectively delivered functional protein cargo, including cytochrome C, to the cytosol of cancer cells in vitro, using hydrophobic ion pairing to improve cargo distribution in the vesicles and release. The globular protein used to make the vesicles can be varied to achieve different functions. For example, enzyme vesicles exhibit biocatalysis, and antigen vesicles induce antibody and cellular immune responses after vaccination in mice. Collectively, the development and engineering of the protein vesicle platform has employed amphiphilic self-assembly strategies and rational protein engineering to control physical, chemical, and biological properties for biotechnology and nanomedicine applications.

Targeted Clindamycin Delivery Systems: Promising Options for Preventing and Treating Bacterial Infections Using Biomaterials

Targeted therapy represents a real opportunity to improve the health and lives of patients. Developments in this field are confirmed by the fact that the global market for drug carriers was worth nearly $40 million in 2022. For this reason, materials engineering and the development of new drug carrier compositions for targeted therapy has become a key area of research in pharmaceutical drug delivery in recent years. Ceramics, polymers, and metals, as well as composites, are of great interest, as when they are appropriately processed or combined with each other, it is possible to obtain biomaterials for hard tissues, soft tissues, and skin applications. After appropriate modification, these materials can release the drug directly at the site requiring a therapeutic effect. This brief literature review characterizes routes of drug delivery into the body and discusses biomaterials from different groups, options for their modification with clindamycin, an antibiotic used for infections caused by aerobic and anaerobic Gram-positive bacteria, and different methods for the final processing of carriers. Examples of coating materials for skin wound healing, acne therapy, and bone tissue fillers are given. Furthermore, the reasons why the use of antibiotic therapy is crucial for a smooth and successful recovery and the risks of bacterial infections are explained. It was demonstrated that there is no single proven delivery scheme, and that the drug can be successfully released from different carriers depending on the destination.

Mitochondria-Selective Dicationic Small-Molecule Ligand Targeting G-Quadruplex Structures for Human Colorectal Cancer Therapy.

Mitochondria are important drug targets for anticancer and other disease therapies. Certain human mitochondrial DNA sequences capable of forming G-quadruplex structures (G4s) are emerging drug targets of small molecules. Despite some mitochondria-selective ligands being reported for drug delivery against cancers, the ligand design is mostly limited to the triphenylphosphonium scaffold. The ligand designed with lipophilic small-sized scaffolds bearing multipositive charges targeting the unique feature of high mitochondrial membrane potential (MMP) is lacking and most mitochondria-selective ligands are not G4-targeting. Herein, we report a new small-sized dicationic lipophilic ligand to target MMP and mitochondrial DNA G4s to enhance drug delivery for anticancer. The ligand showed marked alteration of mitochondrial gene expression and substantial induction of ROS production, mitochondrial dysfunction, DNA damage, cellular senescence, and apoptosis. The ligand also exhibited high anticancer activity against HCT116 cancer cells (IC50, 3.4 μM) and high antitumor efficacy in the HCT116 tumor xenograft mouse model (∼70% tumor weight reduction).

Cryo-Milled β-Glucan Nanoparticles for Oral Drug Delivery

Gemcitabine is a nucleoside analog effective against a number of cancers. However, it has an oral bioavailability of less than 10%, due to its high hydrophilicity and low permeability through the intestinal epithelium. Therefore, the aim of this project was to develop a novel nanoparticulate drug delivery system for the oral delivery of gemcitabine to improve its oral bioavailability. In this study, gemcitabine-loaded β-glucan NPs were fabricated using a film-casting method followed by a freezer-milling technique. As a result, the NPs showed a small particle size of 447.6 ± 14.2 nm, and a high drug entrapment efficiency of 64.3 ± 2.1%. By encapsulating gemcitabine into β-glucan NPs, a sustained drug release profile was obtained, and the anomalous diffusion release mechanism was analyzed, indicating that the drug release was governed by diffusion through the NP matrix as well as matrix erosion. The drug-loaded NPs had a greater ex vivo drug permeation through the porcine intestinal epithelial membrane compared to the plain drug solution. Cytotoxicity studies showed a safety profile of the β-glucan polymers, and the IC50s of drug solution and drug-loaded β-glucan NPs were calculated as 228.8 ± 31.2 ng·mL−1 and 306.1 ± 46.3 ng·mL−1, respectively. Additionally, the LD50 of BALB/c nude mice was determined as 204.17 mg/kg in the acute toxicity studies. Notably, pharmacokinetic studies showed that drug-loaded β-glucan NPs could achieve a 7.4-fold longer T1/2 and a 5.1-fold increase in oral bioavailability compared with plain drug solution. Finally, in vivo pharmacodynamic studies showed the promising capability of gemcitabine-loaded β-glucan NPs to inhibit the 4T1 breast tumor growth, with a 3.04- and 1.74-fold reduction compared to the untreated control and drug solution groups, respectively. In conclusion, the presented freezer-milled β-glucan NP system is a suitable drug delivery method for the oral delivery of gemcitabine and demonstrates a promising potential platform for oral chemotherapy.

Cold Plasma Deposition of Tobramycin as an Approach to Localized Antibiotic Delivery to Combat Biofilm Formation

Hospital-acquired infections (HAIs) remain a significant factor in hospitals, with implant surfaces often becoming contaminated by highly resistant strains of bacteria. Recent studies have shown that electrical plasma discharges can reduce bacterial load on surfaces, and this approach may help augment traditional antibiotic treatments. To investigate this, a cold atmospheric plasma was used to deposit tobramycin sulphate onto various surfaces, and the bacterial growth rate of K. pneumoniae in its planktonic and biofilm form was observed to probe the interactions between the plasma discharge and the antibiotic and to determine if there were any synergistic effects on the growth rate. The plasma-deposited tobramycin was still active after passing through the plasma field and being deposited onto titanium or polystyrene. This led to the significant inhibition of K. pneumoniae, with predictable antibiotic dose dependence. Separate studies have shown that the plasma treatment of the biofilm had a weak antimicrobial effect and reduced the amount of biofilm by around 50%. Combining a plasma pre-treatment on exposed biofilm followed by deposited tobramycin application proved to be somewhat effective in further reducing biofilm growth. The plasma discharge pre-treatment produced a further reduction in the biofilm load beyond that expected from just the antibiotic alone. However, the effect was not additive, and the results suggest that a complex interaction between plasma and antibiotic may be at play, with increasing plasma power producing a non-linear effect. This study may contribute to the treatment of infected surgical sites, with the coating of biomaterial surfaces with antibiotics reducing overall antibiotic use through the targeted delivery of therapeutics.

Methods, Mechanisms, and Application Prospects for Enhancing Extracellular Vesicle Uptake.

Extracellular vesicles (EVs) are considered to be a new generation of bioinspired nanoscale drug delivery systems due to their low immunogenicity, natural functionality, and excellent biocompatibility. However, limitations such as low uptake efficiency, insufficient production, and inhomogeneous performance undermine their potential. To address these issues, numerous researchers have put forward various methods and applications for enhancing EV uptake in recent decades. In this review, we introduce various methods for the cellular uptake of EVs and summarize recent advances on the methods and mechanisms for enhancing EV uptake. In addition, we provide further understanding regarding enhancing EV uptake and put forward prospects and challenges for the development of EV-based therapy in the future.

Dual Drug Delivery for Augmenting Bacterial Wound Complications via Tailored Ultradeformable Carriers.

Addressing the complex challenge of healing of bacterially infected wounds, this study explores the potential of lipid nanomaterials, particularly advanced ultradeformable particles (UDPs), to actively influence the wound microenvironment. The research introduces a novel therapeutic approach utilizing silver sulfadiazine (SSD) coupled with vitamin E (VE) delivered through UDPs (ethosomes/transferosomes/transethosomes). Comparative physicochemical characterization of these nanosized drug carriers reveals the superior stability of transethosomes, boasting a zeta potential of -36.5 mV. This method demonstrates reduced side effects compared to conventional therapies, with almost 90% SSD and 72% VE release achieved in wound pH in a sustained manner. Cytotoxicity assessment shows 60% cell viability even at the highest concentration (175 μg/mL), while hemolysis test demonstrates RBC lysis below 5% at a concentration of 250 μg/mL. Vitamin E-SSD-loaded transethosomes (VSTEs) significantly enhance cellular migration and proliferation, achieving 95% closure within 24 h, underscoring their promising efficacy. The synergistic method effectively reduces bacterial burden, evidenced by an 80% reduction in Escherichia coli and Staphylococcus aureus within the wound microenvironment. This approach offers a promising strategy to address complications associated with skin injuries.

Perspectives of healthcare providers and persons with type 2 diabetes mellitus on improving glycaemic control in Kinshasa, Democratic Republic of the Congo: a qualitative study

IntroductionGlycaemic control remains suboptimal in the Democratic Republic of the Congo. Defining interventions to improve glycaemic control requires a clear knowledge of factors driving poor glycaemic control. Qualitative studies exploring...

Tumor Supplying Artery Injection of Liposome@Sunitinib Could Effectively Inhibit the Progression of Kidney Tumor.

Renal cell carcinoma (RCC) is one of the most common malignancies in the urinary system and is not sensitive to chemotherapy or radiotherapy in its advanced stages. Sunitinib is recommended as a first-line target drug for unresectable and metastatic RCC by targeting tyrosine kinase-related signaling pathways, but its therapeutic effect is unsatisfactory. Recently, nanomaterials have shown great prospects in the medical field because of their unique physicochemical properties. Particularly, liposomes are considered as ideal drug delivery systems due to their biodegradability, biocompatibility, and ideal drug-loading efficiency. Considering that tumor supplying artery injection can directly distribute drugs into tumor tissues, in this study, liposomes were employed to encapsulate water-insoluble sunitinib to construct the liposome@sunitinib (Lipo@Suni) complex, so that the drug could directly target and distribute into tumor tissue, and effectively trapped in tumor tissues after tumor supplying artery injection for the advantage of the physicochemical properties of liposomes, thereby achieving a better therapeutic effect on advanced RCC. Here, we found that compared with the peripheral intravenous administration, trans-renal arterial administration increases the content and prolongs the retention time of liposomes in tumor tissues; accordingly, more sunitinib is dispersed and retained in tumor tissues. Ultimately, trans-renal arterial administration of Lipo@Suni exerts a better suppressive effect on RCC progression than peripheral intravenous administration, even better than the conventional oral administration of sunitinib.

Protein-Mediated Changes in Membrane Fluidity and Ordering: Insights into the Molecular Mechanism and Implications for Cellular Function.

Probing protein-membrane interactions is vital for understanding biological functionality for various applications such as drug development, targeted drug delivery, and creation of functional biomaterials for medical and industrial purposes. In this study, we have investigated interaction of Human Serum Albumin (HSA) with two different lipids, dipalmitoylphosphatidylglycerol (dDPPG) and dipalmitoylphosphatidylcholine (dDPPC), using Vibrational Sum Frequency Generation spectroscopy at different membrane fluidity values. In the liquid-expanded (LE) state of the lipid, HSA (at pH 3.5) deeply intercalated lipid chains through a combination of electrostatic and hydrophobic interactions, which resulted in more ordering of the lipid chains. However, in the liquid-condensed (LC) state, protein intercalation is decreased due to tighter lipid packing. Moreover, our findings revealed distinct differences in HSA's interaction with dDPPG and dDPPC lipids. The interaction with dDPPC remained relatively weak compared to dDPPG. These results shed light on the significance of protein mediated changes in lipid characteristics, which hold considerable implications for understanding membrane protein behavior, lipid-mediated cellular processes, and lipid-based biomaterial design.