Search Results (65)

Background/Objectives: Filamentous fungi, in particular the species Aspergillus, Scedosporium, and Exophiala, frequently colonize the lungs of cystic fibrosis (CF) patients. Chronic colonization is linked to hypersensitivity reactions and persistent infections leading to a significant long-term decline in lung function. Azole antifungal therapy such as voriconazole (VRC) slows disease progression, particularly in patients with advanced CF; however, excessive mucus production in CF lungs poses a diffusional barrier to effective treatment. Methods: Here, biodegradable nanohydrogels (NHGs) recently developed as nanocarriers were evaluated for formulating VRC as a platform for treating fungal infections in CF lungs. The NHGs entrapped up to about 30 μg/mg of VRC, and physicochemical properties were investigated via dynamic laser light scattering and nanoparticle tracking analysis. Diameters were 100–400 nm, and excellent colloidal stability was demonstrated in interstitial fluids, indicating potential for pulmonary delivery. Nano-formulations exhibited high in vitro cytocompatibility in A549 and HEK293T cells and were tested for the release of VRC under two different sink conditions. Results: Notably, the antifungal activity of VRC-loaded nanohydrogels was up to eight-fold greater than an aqueous suspension drug against different fungal species isolated from CF sputum, regardless of the presence of a CF artificial mucus layer. Conclusions: These findings support the development of potent VRC nano-formulations for treating fungal disorders in CF lungs. Full article

Resorbable microparticles can be added to hydrogel-based biocompatible scaffolds to improve their mechanical characteristics and allow localised drug delivery, which will aid in tissue repair and regeneration. It is well-known that bioprinting is important for producing scaffolds personalised to patients by loading them with their own cells and printing them with specified shapes and dimensions. The question is how the addition of such particles affects the rheological responsiveness of the hydrogels (which is critical during the printing process) as well as mechanical parameters like the elastic modulus. This study tries to answer this question using a specific system: an alginate-gelatine hydrogel containing polyhydroxybutyrate-co-hydroxyvalerate (PHBV) microparticles. Scaffolds were made by bioprinting and moulding incorporating PHBV microspheres (7–12 μm in diameter) into alginate–gelatine inks (4.5 to 9.0% w/v). The microparticles (MP) were predominantly located within the polymeric matrix at concentrations up to 10 mg MP/mL ink. Higher particle concentrations disrupted their spatial distribution. Inks pre-crosslinked with 15 mM calcium and containingMPat concentrations ranging from 0 to 10 mg/mL demonstrated rheological characteristics appropriate for bioprinting, such as solid-like behaviour (G′ = 1060–1300 Pa, G″ = 720–930 Pa), yield stresses of 320–400 Pa, and pseudoplastic behaviour (static viscosities of 4000–5600 Pa·s and ~100 Pa·s at bioprinting shear rates). Furthermore, these inks allow high printing quality, assessed through scaffold dimensions, filament widths, and printability (Pr > 0.94). The modulus of elasticity in compression (E) of the scaffolds varied according to the content of MP and the manufacturing technique, with values resembling those of soft tissues (200–600 kPa) and exhibiting a maximum reinforcement effect with 3 mg MP/mL ink (bioprinted E = 273 ± 28 kPa; moulded E = 541 ± 66 kPa). Over the course of six days, the sample’s mass and shape remained stable during degradation in simulated body fluid (SBF). Thus, the alginate–gelatine hydrogel loaded with PHBV microspheres inks shows promise for targeted drug delivery in soft tissue bioengineering applications. Full article

Itraconazole (ITZ), a broad-spectrum triazole antifungal agent, exhibits remarkable pharmacodynamic and pharmacokinetic properties. However, the low solubility of ITZ significantly reduces its oral bioavailability. Furthermore, it has been reported that this medication can result in dose-related adverse effects. Therefore, the objective of this study was to enhance the solubility of ITZ through the utilization of various polymers and to manufacture personalized and programmable release ITZ tablets. Five different polymers were selected as water-soluble carriers. Thirty percent w/w ITZ was mixed with seventy percent w/w of the polymers, which were then extruded. A series of physical and chemical characterization studies were conducted, including DSC, PXRD, PLM, and in vitro drug release studies. The results demonstrated that ITZ was dispersed within the polymers, forming ASDs that markedly enhanced its solubility and dissolution rate. Consequently, soluplus^® was employed as the polymer for the extrusion of ITZ-loaded filaments, which were subsequently designed and printed. The in vitro drug release studies indicated that the release of ITZ could be regulated by modifying the 3D structure design. Overall, this study found that the combination of HME and 3D printing technologies could represent an optimal approach for the development of personalized and precise drug delivery dosages. Full article

Background/Objectives: Three-dimensional printing technology has emerging interest in pharmaceutical manufacturing, offering new opportunities for personalized medicine and customized drug delivery systems. Fused deposition modeling (FDM) is highly regarded in the pharmaceutical industry because of its cost effectiveness, easy operation, and versatility in creating pharmaceutical dosage forms. This review investigates different methods of incorporating active pharmaceutical ingredients (APIs) into filament matrices for use in fused deposition modeling (FDM) 3D printing. Methods: Two electronic databases, the Web of Science and PubMed, were utilized to survey the literature. The selected keywords for this review were as follows: fused filament fabrication OR fused deposition modeling OR FDM OR FFF AND 3D printing AND loading techniques OR impregnation techniques AND solid dosage form. Results: This paper evaluates various loading techniques such as soaking, supercritical impregnation, microwave impregnation, and hot-melt extrusion, focusing on their effectiveness and capacity for drug incorporation. Additionally, this review includes a thorough risk assessment of the extrusion process using Ishikawa and SWOT analyses. Conclusions: Overall, this review provides comprehensive insights into the latest advancements in 3D printing for pharmaceutical applications and identifies key areas for future research and development. Full article

Background: The properties of nanoparticle surfaces are crucial in influencing their interaction with biological environments, as well as their stability, biocompatibility, targeting abilities, and cellular uptake. Hydrophobin 4 (HFB4) is a class II HFB protein produced by filamentous fungi that has a natural ability to self-assemble at hydrophobic-hydrophilic interfaces. The biocompatible, non-toxic, biodegradable, and amphipathic properties of HFB4 render it valuable for improving the solubility and bioavailability of hydrophobic drugs. We have investigated the physicochemical properties, cellular uptake, and anticancer effects of empty and Doxorubicin (Dox)-loaded HFB4 liposomes (HFB4L) and compared them to those of PEGylated liposomes (PPL). Methods: The Pichia pastoris KM71H strain was used for HFB4 purification. Liposomes were prepared through the thin film hydration method and characterized. The cytotoxic effects of free Dox, Dox-HFB4, and Dox-PPL were assessed in MCF7 cells using the SRB Assay. Results: All formulations showed good size homogeneity and a spherical shape. The HFB4 coating enhanced the physicochemical stability of Dox-HFB4L over 60 days at 4 °C without significantly affecting Dox release from HFB4L. It increased Dox release at pH 5.4 compared to pH 7.4, indicating higher delivery of drugs into acidic tumor environments, similar to Dox-PPL. While both formulations showed increased cellular uptake compared to free Dox, they exhibited a lower anticancer effect due to the sustained release of Dox. Notably, Dox-HFB4L displayed greater cytotoxicity than Dox-PPL in MCF7 cells. Conclusions: HFB4L may offer superior benefits in terms of delivering drugs to an acidic tumor environment in a stable, non-toxic, and sustained manner. Full article

Fiber-based technologies are widely used in various industries, but their use in pharmaceuticals remains limited. While melt extrusion is a standard method for producing medical fibers such as sutures, it is rarely used for pharmaceutical fiber-based dosage forms. The EsoCap system is a notable exception, using a melt-extruded water-soluble filament as the drug release trigger mechanism. The challenge of producing drug-loaded fibers, particularly due to the use of spinning oils, and the processing of the fibers are addressed in this work using other approaches. The aim of this study was to develop processes for the production and processing of pharmaceutical fibers for targeted drug delivery. Fibers loaded with polyvinyl alcohol and fluorescein sodium as a model drug were successfully prepared by a continuous melt extrusion process and directly spun. These fibers exhibited uniform surface smoothness and consistent tensile strength. In addition, the fibers were further processed into tubular dosage forms using a modified knitting machine and demonstrated rapid drug release in a flow cell. Full article

Sulforaphane (SFN) has shown potential as an antioxidant and anti-inflammatory agent. To improve its druggability, we developed new analgesic formulations with sulforaphane-loaded hyaluronic acid (HA)-poloxamer (PL) hydrogel. This study evaluated the pre-clinical safety and effectiveness of these formulations. Effectiveness was tested on Wistar rats divided into groups (n = 15) receiving (IM, 10 mg/kg) SFN formulations or control groups (without SFN). This study used a hind paw incision postoperative pain model to evaluate mechanical hypersensitivity with von Frey filaments. TNF-α, IL-1β, substance P, and CGRP levels verified anti-inflammatory activity in the hind paw tissue. Histopathology of tissues surrounding the injection site was assessed after 2 and 7 days post-treatment. To corroborate drug safety, cell viability of 3T3 and RAW 264.7 cultures was assessed. Additionally, RAW 264.7 cultures primed with carrageenan evaluated nitric oxide (NO) levels. All animals exhibited post-incisional hypersensitivity, and F2 (PL 407/338 (18/2%) + HA 1% + SFN 0.1%) showed a longer analgesic effect (p < 0.05). F2 reduced TNF-α, IL-1β, and CGRP levels (p < 0.05). Histopathological evaluation showed mild to moderate inflammatory reactions after the formulations’ injections. F2 produced no significant difference in cell viability (p > 0.05) but reduced NO production (p < 0.05). Thus, our results highlight the biocompatibility and effectiveness of F2. Full article

This work aimed to develop a three-dimensional (3D) wearable drug-loaded earring tap to treat affections caused by aesthetic perforations. The initial phase involved a combination of polymers to prepare filaments for fused deposition modeling (FDM) 3D printing using a centroid mixture design. Optimized filament compositions were used in the second phase to produce 3D printed earring taps containing the anti-inflammatory naringenin. Next, samples were assessed via physicochemical assays followed by in vitro skin permeation studies with porcine ear skin. Two filament compositions were selected for the study’s second phase: one to accelerate drug release and another with slow drug dissolution. Both filaments demonstrated chemical compatibility and amorphous behavior. The use of the polymer blend to enhance printability has been confirmed by rheological analysis. The 3D devices facilitated naringenin skin penetration, improving drug recovery from the skin’s most superficial layer (3D device A) or inner layers (3D device B). Furthermore, the devices significantly decreased transdermal drug delivery compared to the control containing the free drug. Thus, the resulting systems are promising for producing 3D printed earring taps with topical drug delivery and reinforcing the feasibility of patient-centered drug administration through wearable devices. Full article

Limitations of bone defect reconstruction include poor bone healing and osteointegration with acrylic cements, lack of strength with bone putty/paste, and poor osteointegration. Tissue engineering aims to bridge these gaps through the use of bioactive implants. However, there is often a risk of infection and biofilm formation associated with orthopedic implants, which may develop anti-microbial resistance. To promote bone repair while also locally delivering therapeutics, 3D-printed implants serve as a suitable alternative. Soft, nanoporous 3D-printed filaments made from a thermoplastic polyurethane and polyvinyl alcohol blend, LAY-FOMM and LAY-FELT, have shown promise for drug delivery and orthopedic applications. Here, we compare 3D printability and sustained antibiotic release kinetics from two types of commercial 3D-printed porous filaments suitable for bone tissue engineering applications. We found that both LAY-FOMM and LAY-FELT could be consistently printed into scaffolds for drug delivery. Further, the materials could sustainably release Tetracycline over 3 days, independent of material type and infill geometry. The drug-loaded materials did not show any cytotoxicity when cultured with primary human fibroblasts. We conclude that both LAY-FOMM and LAY-FELT 3D-printed scaffolds are suitable devices for local antibiotic delivery applications, and they may have potential applications to prophylactically reduce infections in orthopedic reconstruction surgery. Full article

Background: Beauveria bassiana is a filamentous fungus commonly used as an insecticide that rarely causes keratitis. Methods: Patients affected by Beauveria bassiana keratitis were retrospectively recruited at San Raffaele Hospital (Milan, Italy) between 2020 and 2022. All subjects underwent comprehensive ophthalmic evaluation, including in vivo confocal microscopy (IVCM) and microbiologic examination of corneal scrapings. Beauveria bassiana was identified using 18S rDNA targeted PCR. Results: Four eyes of four patients (51 ± 8.8 years old) were evaluated. The main risk factors were soft contact lens wear (75%) and trauma with vegetative matter (50%). A superficial infiltrate was displayed in the majority of patients. Three cases (75%) showed hyphae on IVCM. All patients showed clinical improvement after topical antifungal therapy, although mostly through a combination of two antifungals (75%). One patient with a deeper infection required a systemic antifungal agent after one month of topical therapy. All cases required debridement to reduce the microbial load and enhance drug penetration. All patients experienced keratitis resolution following medical treatment (average: 3.3 months). Conclusions: The identification of risk factors and the early diagnosis of Beauveria bassiana keratitis are fundamental in order to avoid its penetration in the deeper corneal stromal layers. Topical antifungal drugs, possibly accompanied by ulcer debridement, may be a successful treatment if instilled from the early phases of the disease. Full article

Dual-nozzle fused deposition modeling (FDM) is a 3D printing technique that allows for the simultaneous printing of two polymeric filaments and the design of complex geometries. Hence, hybrid formulations and structurally different sections can be combined into the same dosage form to achieve customized drug release kinetics. The objective of this study was to develop a novel bicompartmental device by dual-nozzle FDM for colon-specific drug delivery. Hydroxypropylmethylcellulose acetate succinate (HPMCAS) and polyvinyl alcohol (PVA) were selected as matrix-forming polymers of the outer pH-dependent and the inner water-soluble compartments, respectively. 5-Aminosalicylic acid (5-ASA) was selected as the model drug. Drug-free HPMCAS and drug-loaded PVA filaments suitable for FDM were extruded, and their properties were assessed by thermal, X-ray diffraction, microscopy, and texture analysis techniques. 5-ASA (20% w/w) remained mostly crystalline in the PVA matrix. Filaments were successfully printed into bicompartmental devices combining an outer cylindrical compartment and an inner spiral-shaped compartment that communicates with the external media through an opening. Scanning electron microscopy and X-ray tomography analysis were performed to guarantee the quality of the 3D-printed devices. In vitro drug release tests demonstrated a pH-responsive biphasic release pattern: a slow and sustained release period (pH values of 1.2 and 6.8) controlled by drug diffusion followed by a faster drug release phase (pH 7.4) governed by polymer relaxation/erosion. Overall, this research demonstrates the feasibility of the dual-nozzle FDM technique to obtain an innovative 3D-printed bicompartmental device for targeting 5-ASA to the colon. Full article

The manufacture of medicines on demand for a particular patient, at the point of care, may be achieved via 3D printing, improving therapeutic outcomes, medication adherence and patient safety. Tablets are often printed using a combination of hot-melt extrusion and fused deposition modelling. In this work, paracetamol-loaded hydroxypropylcellulose filaments were produced; their extrudability and printability were aided by a plasticizer and a lubricant. For printability, 11% humidity was the ideal storage condition for filaments up to 6 months. The tablets produced complied with the uniformity of mass and content requirements, and showed delayed drug release; these characteristics were maintained after in-use stability testing for 30 days. Full article

Three-dimensional-printed customizable drug-loaded implants provide promising opportunities to improve the current therapy options. In this study, we present a modular implant in which shape, dosage, and drug release can be individualized independently of each other to patient characteristics to improve parenteral therapy with triamcinolone acetonide (TA) over three months. This study focused on the examination of release modification via fused deposition modeling and subsequent prediction. The filaments for printing consisted of TA, ethyl cellulose, hypromellose, and triethyl citrate. Two-compartment implants were successfully developed, consisting of a shape-adaptable shell and an embedded drug-loaded network. For the network, different strand widths and pore size combinations were printed and analyzed in long-term dissolution studies to evaluate their impact on the release performance. TA release varied between 8.58 ± 1.38 mg and 21.93 mg ± 1.31 mg over three months depending on the network structure and the resulting specific surface area. Two different approaches were employed to predict the TA release over time. Because of the varying release characteristics, applicability was limited, but successful in several cases. Using a simple Higuchi-based approach, good release predictions could be made for a release time of 90 days from the release data of the initial 15 days (RMSEP ≤ 3.15%), reducing the analytical effort and simplifying quality control. These findings are important to establish customizable implants and to optimize the therapy with TA for specific intra-articular diseases. Full article

The present study aimed to develop 3D printed dosage forms, using custom-made filaments loaded with diclofenac sodium (DS). The printed tablets were developed by implementing a quality by design (QbD) approach. Filaments with adequate FDM 3D printing characteristics were produced via hot melt extrusion (HME). Their formulation included DS as active substance, polyvinyl alcohol (PVA) as a polymer, different types of plasticisers (mannitol, erythritol, isomalt, maltodextrin and PEG) and superdisintegrants (crospovidone and croscarmellose sodium). The physicochemical and mechanical properties of the extruded filaments were investigated through differential scanning calorimetry (DSC), X-ray diffraction (XRD) and tensile measurements. In addition, cylindrical-shaped and tubular-shaped 3D dosage forms were printed, and their dissolution behaviour was assessed via various drug release kinetic models. DSC and XRD results demonstrated the amorphous dispersion of DS into the polymeric filaments. Moreover, the 3D printed tablets, regardless of their composition, exhibited a DS release of nearly 90% after 45 min at pH 6.8, while their release behaviour was effectively described by the Korsmeyer–Peppas model. Notably, the novel tube design, which was anticipated to increase the drug release rate, proved the opposite based on the in vitro dissolution study results. Additionally, the use of crospovidone increased DS release rate, whereas croscarmellose sodium decreased it. Full article

Three-dimensional (3D) printing has emerged as a new promising technique for the production of personalized dosage forms and medical devices. Polyvinyl alcohol is prominently used as a source material to produce 3D-printed medicines via fused deposition modeling (FDM)—a technology that combines hot melt extrusion and 3D printing. A preliminary screening of three grades of PVA indicated that partially hydrolyzed PVA with a molecular weight (MW) of 31,000–50,000 and plasticized with sorbitol was most suitable for 3D printing. Paracetamol was used as a model drug. The materials and the produced filaments were characterized by X-ray powder diffraction (XRPD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The complex viscosity (η*) of the polymer melts was determined as a function of the angular frequency (ω) at the printing temperature to assess their printability. Three-dimensional printlets with a 40% infill exhibited an immediate release of the API, while tablets with a higher infill were prone to a prolonged release regardless of the filament drug loading. A factorial design was used to give more insight into the influence of the drug-loading of the filaments and the tablet infill as independent variables on the production of 3D printlets. The Pareto chart confirmed that the infill had a statistically significant effect on the dissolution rate after 45 min, which was chosen as the response variable. Full article