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.

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.

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.

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.

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

Rheumatoid arthritis is a chronic autoimmune disease, progressively distinctive via cartilage destruction, auto-antibody production, severe joint pain, and synovial inflammation. Nanotechnology represents one of the utmost promising scientific technologies of the 21^st century. Nanocarriers could be the key to unlocking its potential by encapsulating Rutin in targeted drug delivery systems, potentially for targeted Rheumatoid arthritis therapy.

The rationale of current research is to prepare liposomes loaded with a bioflavonoid drug rutin for effective management of rheumatoid arthritis.

This study investigated the formulation of rutin liposomes using the thin-film hydration technique, also known as the Bangham method. A Box-Behnken design was employed to optimize the formulation parameters. The LP2 batch was then characterized for its mean particle size, zeta potential, shape, diffraction pattern, and thermal properties. Finally, the in-vitro anti-oxidant and anti-inflammatory potential of the rutin liposomes were evaluated using appropriate assays.

Out of thirteen batches, LP2 was found to be an optimized batch with a mean particle size of 167.1 nm, zeta potential -13.50 mV, and entrapment efficiency of 61.22%. The above results showed higher stability of rutin liposomes. Further characterization of LP2 for morphological assessment, XRD analysis, and DSC revealed its spherical shape less than 1 µm, polycrystalline nature, and thermographic peak at 139°C, respectively. Evaluation of the antioxidant properties and anti-inflammatory potential of LP2 revealed its maximum therapeutic potential in the reduction of inflammation and protein denaturation when evaluated via in-vitro assays.

Rutin liposomal formulation has tremendous potential for the management of Rheumatoid arthritis due to its enhanced bioavailability, anti-oxidant, and anti-inflammatory properties when compared to free rutin.

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.

The spread of tumors (48% in men and 51% in women), as well as the protection of malignant tumors by stromal cells and complex blood vessels, pose significant challenges to drug delivery to tumors. Modern chemotherapy, on the other hand, addresses tumor growth suppression by at least 60% through versatile formulation systems and numerous modifications to drug delivery systems. The renewable and naturally occurring polymers present invariably in all living cells form the fundamental foundation for most anticancer drug development. The review aims to discuss in detail the preparations of polysaccharide, lipid, and protein-based drug-loading vehicles for the targeted delivery of prominent anticancer drugs. It also provides an explanation of drug distribution in blood (cumulative releases of nearly 80% drug) and drug accumulation at tumor sites (1–5 mg/kg) due to enhanced permeability and retention (EPR).

Specific delivery examples for treating colorectal and breast carcinomas have been presented to distinguish the varied drug administration, bioavailability, and tumor internalization mechanisms between sugar, fatty acid, and amino acid polymers. Current therapy possibilities based on cutting-edge literature are provided, along with drug delivery systems tailored to tumor location and invasive properties.

The unique combinations of the three natural polymers provide unparalleled solutions to minimize the toxicity (<20% drug release) of the chemotherapeutic drugs on normal tissues. Moreover, the development of a consolidated drug delivery system has contributed to a substantial reduction (dose reduction from 10.43 µM to 1.9 µM) in the undesirable consequences of higher dosages of chemotherapeutic drugs.

The review extensively covers safe chemotherapeutic systems with significant advantages (tumor volume shrinkage of 4T1 cells from 1000 mm³ to 200 mm³) in clinical applications of carcinoma treatments using natural polymers.

The last strategy in targeted drug delivery systems is to deliver the anticancer drug to the tumor tissue to increase its therapeutic effect and minimize its undesirable side effects. In line with this goal in this research, the redox/pH-responsive disulfide magnetic nanocarriers based on PF127-NH2/L-cysteine-CM-β-CD-FA were synthesized and evaluated in a doxorubicin delivery system.

We effectively surrounded Fe3O4 nanoparticles with SiO2 using the sol-gel method, and then confidently coated them with oleic acid on Fe3O4@SiO2 nanoparticles.. In another reaction, a PF127-NH2/L-cysteine-CM-β-CD-FA was synthesized. The process involved modifying pluronic F127 (PF 127) with maleic anhydride and aminating it to form PF127-NH2. The obtained PF127-NH2 was attached to L-cysteine, followed by condensing with carboxymethyl-β-cyclodextrin and then functionalized by folic acid. Finally, PF127-NH2/L-cysteine-CM-β-CD-FA was coated on the surface of magnetic nanoparticles, and the resulting PF127-NH2/L-cysteine-CM-β-CD-FA was disulfidated to form the final nanocarrier network, which was abbreviated as LCMNPs-SS. The doxorubicin was used as a model drug and loaded into the LCMNPs-SS nanocarrier.

The LCMNPs-SS nanocarrier exhibited excellent properties for controlled release, with a well-defined release rate, a controllable level by an external magnet, and adjusting by DL-dithiothreitol concentration. The LCMNPs-SS nanocarrier could also break apart when exposed to an oxidant or a change in pH. This meant that the drug release could be fine-tuned in response to temperature, pH, or more than one stimulus.

These drug-carrying systems are valuable in reducing the dose of doxorubicin. High internalization of the synthesized LCMNPs-SS caused sped cellular uptake.