Current Drug Delivery - Online First

Methicillin-Resistant Staphylococcus Aureus (MRSA) is a major cause of purulent Skin and Soft-Tissue Infections (SSTIs), posing significant global health and economic challenges. This study aims to optimize a drug delivery system, specifically Tigecycline-loaded transfersomes, to address the limitations of current treatments, including bacterial resistance, systemic side effects, and poor drug penetration, thereby offering a safer and more effective alternative for MRSA-related SSTIs.

A novel Tigecycline transfersomal formulation was developed using the thin film hydration method. The study investigated the effects of varying drug-to-lipid ratios, lipid-to-edge activator ratios, and different hydration media on the characteristics of the Tigecycline-loaded transfersomes. The formulation’s morphology, release profile, and antibacterial activity against clinical MRSA strains were also evaluated.

The Tigecycline-loaded transfersomes were successfully prepared with particle sizes ranging from 92.3 to 290.8 nm, zeta potential values from -16.22 to -48.7 mV, and encapsulation efficiencies ranging from 54.8% to 84.39%. The formulation prepared using distilled water as the hydration medium, a lipid-to-edge activator ratio of 80:20, and a drug-to-lipid ratio of 3:8 was selected for further assessment due to its optimal characteristics. The selected transfersomes were spherical with an average diameter of 131 nm. The formulation exhibited a controlled drug release profile and demonstrated a twofold increase in antibacterial activity against MRSA compared to non-liposomal Tigecycline.

The results highlighted the significant role of formulation parameters in tailoring transferosomal characteristics and enhancing therapeutic performance. The study builds on existing research by introducing Tigecycline—a broad-spectrum antibiotic—into transfersomal systems for the first time. However, further in vivo validation is necessary.

Tigecycline-loaded transfersomes demonstrated improved drug delivery and antibacterial efficacy against MRSA. This novel formulation shows promise as an effective topical therapy for antibiotic-resistant SSTIs.

One of the least invasive, recognized potential routes for both local and systemic drug delivery and the most patient-friendly methods of administering therapeutic agents is transdermal drug delivery. It minimizes gastrointestinal side effects, prevents hepatic first-pass metabolism, lowers dosage frequency, and boosts patient compliance.

This review aims to examine the nanostructured systems for transdermal drug delivery, focusing on their types, design, development and mechanism in enhancing drug permeation through the skin.

This review article synthesized findings from recent studies on nanostructured systems used in transdermal drug delivery systems. With a particular focus on offering a comprehensive understanding of transdermal drug delivery methods and augmentation strategies, the author examines current trends and potential uses of transdermal technologies.

Nanostructured systems have shown increased drug penetration, improved bioavailability and controlled release profiles.

Nanostructured systems offer a versatile and effective approach to overcoming the limitations of traditional transdermal drug delivery methods. Future research should focus on optimizing these systems for clinical applications, ensuring safety and regulatory compliance.

Hepatocellular carcinoma (HCC) is the sixth most common malignant cancer worldwide, but the chemotherapy drugs used in the treatment of HCC patients have limited efficacy and cause severe side effects. To improve HCC treatment outcomes, a cancer cell membrane (CCM)-coated biomimetic nanodelivery system was designed to achieve enhanced anti-HCC effects.

Poly (lactic-co-glycolic acid) (PLGA) was used to carry both sorafenib, which is used to treat advanced HCC, and superparamagnetic iron oxide nanoparticles (SPIONs). The prepared nanoparticles (NPs) were coated with Huh-7 cell membranes to obtain biomimetic nanoparticles (SFINPs@CCM). The physicochemical properties of SFINPS@CCM were then characterized, and the drug loading efficiency, release rate, transverse relaxation rate for MRI, fluorescence targeting ability, and anti-HCC ability were evaluated.

The SFINPS@CCM were successfully prepared. The loading efficiency of sorafenib in the SFINPs was 88.24%. The cumulative amount of sorafenib released from the SFINPs@CCM at 72 h was 72.96%. In vitro magnetic resonance imaging (MRI) showed the transverse relaxation rate was 25.448 mM⁻¹ s⁻¹. Meanwhile, the fluorescent tracing verified the homologous targeting ability of SFINPs@CCM to Huh-7 cells. The cytotoxicity of SFINPS@CCM was 29.48±5.74%, which was significantly higher than that of the SFINPs.

The study indicates that the SFINPs@CCM system achieves efficient drug delivery and enhances anti-HCC efficacy. While the results are encouraging, further research is needed to confirm broader applicability.

The biomimetic nanodelivery system exhibits good targeting and excellent therapeutic effects, laying a technical foundation for preclinical studies.

This study aims to fabricate dual drug-loaded nanofibrous films made from polyvinyl alcohol (PVA) and chitosan, incorporating cefadroxil and mupirocin to meet the critical needs of burn wound care.

Electrospinning was utilized to fabricate cefadroxil- and mupirocin-loaded polyvinyl alcohol PVA/Chitosan nanofibers. Characterization of structural and morphological properties of these nanofibers was done through Fourier Transform IR Spectroscopy, Scanning Electron Microscopy, Thermal analysis by TGA, and XRD spectroscopy. The kinetic profiles of the drug release mechanisms were considered to determine the release of cefadroxil and mupirocin. Antibacterial activity was determined against the bacteria Staphylococcus aureus and Pseudomonas aeruginosa, while the wound healing efficacy was tested in a rabbit model using full-thickness wounds.

SEM analysis demonstrated the formation of uniform and smooth nanofibers possessing a well-defined morphology. FTIR spectroscopy confirmed the successful incorporation of cefadroxil and mupirocin into the PVA/Chitosan matrix. TGA analysis indicated the thermal stability of the nanofibers, while XRD results suggested that the drugs were either molecularly dispersed or in an amorphous state within the biopolymeric blend. Drug release studies showed distinct profiles, with an initial burst release followed by sustained drug release. Over 80% of mupirocin was released within the first 2 hours, while cefadroxil exhibited a cumulative release exceeding 60%. Antibacterial assays showed significant inhibition zones, with the largest being 20 mm against Staphylococcus aureus. In vivo studies utilizing a full-thickness rabbit wound model revealed that the drug-loaded nanofibers accelerated wound contraction, achieving approximately 90% closure by day 17, compared to less than 70% for the control.

The dual drug-loaded PVA/Chitosan nanofiber films demonstrated excellent antibacterial efficacy and improved wound healing, indicating their therapeutic potential for burn wound management. The combination of cefadroxil and mupirocin within the nanofiber matrix enabled rapid initial drug release followed by sustained delivery, contributing to effective infection control and tissue regeneration.

The study demonstrates that cefadroxil-mupirocin nanofiber films provide superior antibacterial activity and faster wound healing rates, highlighting their potential in advanced burn wound management.

Nanofiber (NF) films have emerged as a promising alternative for treating psoriasis. Based on their specific characteristics, they have distinguished themselves from other topical dosage forms, such as hydrogels, foams, and sponges. This research looks at making biocompatible and biodegradable nanofibers out of polyvinyl alcohol (PVA) and gelatin and adding hesperidin (HPN) and ofloxacin (OFX) as medicine.

HPN-OFX-integrated nanofiber (HPN-OFXNF) films were prepared using electrospinning. Subsequently, the surface morphology, entrapment efficiency, in vitro drug diffusion, and antimicrobial, anti-inflammatory, and anti-psoriasis properties were investigated.

Scanning electron microscopy (SEM) analysis revealed that the produced nanofibers exhibited smooth surfaces with diameters from 50.67 to 114.4 nm, entrapment efficiencies from 69.3 ± 1.8% for OFX and 45.63 ± 1.6% for HPN. At the end of 48 h, nanofibers showed 90.8 ± 2.4% of OFX and 97.3± 3.1% of HPN release. In vitro, antimicrobial testing of the films demonstrated 24.89 ± 3.2 and 42.46 ± 4.4 mm zones of inhibition against E. coli and S. aureus. The total antioxidant activity of HPN is 198.67±2.38 (µ mol AAE/mg HPN), and HPN-OFXNF is 271.12 ± 3.56 (µ mol AAE/mg HPN-OFXNF), and their IC50 values against HaCaT cell growth of 80.5 ± 2.5 and 64.6 ± 3.4 µg/ml, respectively.

HPN-OFXNFs have been developed successfully by the electrospinning method with moderate entrapment efficiencies, showing a biphasic trend of an early burst trailed by a sustained pattern of drug release, depending on the surface area and diameter of the fibers. Enhanced zones of inhibition and anti-inflammatory efficacy of NFs in comparison with their pure counterparts have been demonstrated to be beneficial. Stronger antioxidant efficacy, inducing anti-proliferation and promoting apoptosis in human keratinocytes, has made them the best versions over pure drug compounds.

This therapy, which includes a combined anti-inflammatory and antibacterial treatment strategy with an innovative drug delivery system, has proven to be a promising development in treating psoriasis.

A serious public health condition called liver fibrosis can cause cirrhosis, cancer, and even patient death.

This study sought to determine if Luteolin (LUT) and Silibinin (SBN) could protect rats against oxidative stress and liver fibrosis caused by thioacetamide (TAA) over three weeks, as well as any potential mechanisms of action. There will be 49 adult Wistar albino rats utilized, split up into 7 groups: (G1) Negative control, (G2) Positive control, (G3) LUT+TAA, (G4) SBN+TAA, (G5) mix LUT+ SBN, (G6) LUT+SBN with TAA, (G7) LUT+SBN then TAA, and so. Liver function tests and oxidative stress markers were measured after the experiment. The liver underwent microscopic inspection. Rats given TAA treatment had significantly higher liver enzymes than control; yet, albumin (ALB), total protein (TP), superoxide dismutase (SOD), and reduced glutathione (GSH) significantly decreased.

Following three weeks of TAA exposure, liver sections revealed hepatocytic damage and fibrosis. Oxidative stress, histological alterations, and alterations in liver function were all lessened in TAA rats administered with LUT, SBN, or both.

The combined hepatoprotective benefits of LUT and SBN prevented TAA-induced biochemical and histological alterations in rat liver, acting in concert with each other.

There is a strong need for drug delivery systems that are both highly compatible with biological tissues and effective when used in the oral mucosa. While gels, creams, or ointments are currently employed for this purpose, their oral bioavailability is constrained by the limited contact time with mucosal tissue.

In response to this challenge, we developed and evaluated the efficacy of a multilayer mucoadhesive system incorporated with Dexamethasone Sodium Phosphate (DEX-P) for oral mucosal delivery. An electrospun multilayer system was created and subjected to biocompatibility and efficacy testing via in vitro and ex vivo approaches, finally culminating in an acceptability trial in healthy human volunteers. The multilayer system was created using Poly-Vinyl Pyrrolidone (PVP) and Poly ε-Caprolactone (PCL) as a polymeric base and Polycarbophil (NOVEON® AA-1, PCF) serving as an adhesion enhancer to facilitate the unidirectional release of Dexamethasone Sodium Phosphate (DEX-P).

The nanofibers matrices underwent morphological characterization by Scanning Electron Microscopy (SEM), and DEX-P release was evaluated using ex vivo porcine mucosa, yielding promising results. In vitro cytotoxicity was evaluated through the MTT assay, employing HFF-1 cells. The cell viability ranged from 78 to 96%, suggesting the safety of the polymers used. The tested dose range of DEX on cell lines did not decrease below 75%, indicating its safety in terms of in vivo cytotoxicity. Biocompatibility was evaluated on animal models, without significant tissue damage observed.

The results of this study demonstrate the potential of the developed multilayer mucoadhesive system as an effective platform for oral mucosal drug delivery. The combination of PVP and PCL provides a stable and tunable matrix for drug incorporation, while PCF successfully enhances mucoadhesion and controlled drug release. The electrospun architecture enables precise drug loading and unidirectional release, which is crucial for minimizing systemic absorption and maximizing local therapeutic effects. The high cell viability observed in vitro and the absence of significant tissue damage in vivo underline the biocompatibility of the system. Moreover, the positive feedback from human volunteers not only indicates functional efficacy but also practical usability, which is essential for clinical translation. Taken together, these findings support the feasibility of using this multilayer nanofiber system as a safe and effective vehicle for oral mucosal therapy, particularly for localized delivery of corticosteroids, such as DEX-P.

Human in vivo studies demonstrated prolonged adhesion and a favorable perception of the system.