Current Drug Delivery - Online First

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.

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.

The primary aim of this study was to develop an effective treatment strategy for periodontal diseases that maximizes therapeutic effects while minimizing systemic adverse effects. Specifically, the study focused on creating a xerogel-based localized drug delivery system for the slow release of doxycycline hyclate (DH) to treat periodontal disease.

Xerogels were prepared using the solvent casting method, with the solvent being evaporated slowly at ambient conditions. The prepared DH xerogels underwent comprehensive characterization to assess their in-silico compatibility, pharmacokinetics, and physicochemical properties. The properties studied included drying time and rate, thickness, moisture content, swelling index, organoleptic properties, scanning electron microscopy, FTIR spectroscopy, differential scanning calorimetry, drug release and kinetics, and antibacterial activity.

In-silico studies demonstrated compatibility between the ingredients, indicating minimal adverse effects on the body. The analysis revealed hydrogen bonding between the drug and polymers, changing the drug's crystallization characteristics to an amorphous form. The release profiles of DH from the xerogels indicated a slow release, ranging from 29.42% to 66.30% over 10 hours, following the Hopfenberg model.

The findings of this study suggest that the formulated xerogels are well-suited for periodontal applications. The slow-release profile of DH from the xerogels offers a promising approach for localized treatment of periodontal disease, reducing the risk of systemic adverse effects. This data is valuable for dental practitioners and pharmaceutical formulators, providing a new avenue for enhancing periodontal disease treatment.

Influenza, a seasonal infectious disease, has consistently posed a formidable challenge to global health in recent years. Favipiravir, an RNA-dependent RNA polymerase inhibitor, serves as an anti-influenza medication, currently administered solely in oral form for clinical use. However, achieving an effective therapeutic outcome often necessitates high oral doses, which can be accompanied by adverse effects and suboptimal patient adherence.

To enhance favipiravir delivery efficiency and potentially mitigate dosage-related side effects, this study aimed to formulate favipiravir as a dry powder for pulmonary inhalation, facilitating direct targeting of lung tissue.

Employing L-leucine as a carrier, favipiravir was prepared as an inhalable dry powder through the spray-drying technique. A 3x3 full-factorial design approach was adopted to optimize the formulation. The optimized spray-dried powder underwent comprehensive characterization, including assessments of its morphology, crystallinity, flowability, and aerodynamic particle size distribution. The therapeutic efficacy of the powder was evaluated in a mouse model infected with the H1N1 influenza virus.

The formulated powder demonstrated good aerosol properties, rendering it suitable for inhalation delivery. Its therapeutic efficacy was demonstrated in the mouse model, where it exhibited marked protective effects against the virus in vivo after 5 days of treatment. Notably, the inhalation dose required (15 mg/kg/day) was significantly lower than the oral gavage dose (150 mg/kg/day), indicating that substantially reduced doses, when administered via inhalation, were sufficient to confer protection against mortality in mice.

The findings underscore the potential of inhalation therapy using spray-dried favipiravir powder as an effective and efficient treatment option for influenza, offering the promise of reduced dosing requirements and associated adverse effects.

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.

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.