3D printing has been introduced as a novel approach for the design of personalized dosage forms and support patient groups with special needs that require additional assistance for enhanced medication adherence. In this study liquid crystal display (LCD) is introduced for the development of sustained release bupropion.HCl printed tablets. The optimization of printing hydrogel inks was combined with the display of Braille patterns on the tablet surface for blind or visually impaired patients. Due to the high printing accuracy, the Braille patterns could be verified by blind patients and provide the required information. Further characterization revealed the presence of BUP in amorphous state within the photopolymerized resins. The selection of poly(ethylene glycol) (PEG)-diacrylate (PEGDA) of different molecular weights and the presence of surfactants or solubilizers disrupted the resin photopolymerization, thus controlling the BUP dissolution rates. A small batch scale-up study demonstrated the capacity of LCD to print rapidly a notable number of tablets within 24 min.

The result of infection of bone with microorganisms is osteomyelitis and septic arthritis. Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for most of its cases (more than 50%). Since MRSA is resistant to many treatments, it is accompanied by high costs and numerous complications, necessitating more effective new treatments. Recently, development of gelatin nanoparticles have attracted the attention of scientists of biomedicine to itself, and have been utilized as a delivery vehicle for antibiotics because of their biocompatibility, biodegradability, and cost-effectiveness. Promising results have been reported with gelatin modification and combinations with chemical agents. Although these findings have been suggested that gelatin has the potential to be a suitable option for continuous release of antibiotics in osteomyelitis and septic arthritis treatment, they still have not become routine in clinical practices. The most deliver antibiotic using gelatin-derived composites is vancomycin which is showed the good efficacy. To date, a number of pre-clinical studies evaluated the utility of gelatin-based composites in the management of osteomyelitis. Gelatin-based composites were found to have satisfactory performance in the control of infection, as well as the promotion of bone defect repair in chronic osteomyelitis models. This review summarized the available evidence which provides a new insight into gelatin-derived composites with controlled release of antibiotics.

Oxidative stress has long been known as a pathogenic factor of ulcerative colitis. Superoxide dismutase (SOD) has been demonstrated to mitigate gut mucosal injury via combating oxidative stress. Herein, we developed SOD-loaded multivesicular liposomes (S-MVLs) as sustained-release depot for ulcerative colitis treatment. S-MVLs were spherical honeycomb-like particles with average particle size of 27.3 ± 5.4 μm and encapsulating efficiency of 78.7 ± 2.6 %. Moreover, the two-phase release profiles of SOD from S-MVLs were exhibited, that was, the burst release phase within 4 h and the sustained-release phase within 96 h. After intraperitoneally injecting S-MVLs, in situ retention time of SOD at bowel cavity extended by 4-fold in comparison with SOD solution. In vitro cells experiment showed that S-MVLs had the protective effect on LPS-treated RAW 264.7 cells via scavenging ROS and inhibiting pro-inflammatory cytokines production. S-MVLs ameliorated the body weight loss, DAI score and the colon shortening of colitis mice. Meanwhile, the colonic morphology and the epithelial barrier of colitis mice were effectively recovered after S-MVLs treatment. The therapeutic mechanism might be associated with polymerizing M1 macrophages to M2 phenotypes and alleviating oxidative stress. Collectively, multivesicular liposomes might be a promising sustained-release depot of SOD for ulcerative colitis treatments.

We present the development and characterization of a nasal drug delivery system comprised of a thermosensitive mucoadhesive hydrogel based on a mixture of the polymers Poloxamer 407, Poloxamer 188 and Hydroxypropyl-methylcellulose, and the psychedelic drug 5-methoxy-N,-N-dimethyltryptamine. The development relied on a 3 × 3 Box-Behnken experimental design, focusing on optimizing gelification temperature, viscosity and mucoadhesion. The primary objective of this work was to tailor the formulation for efficient nasal drug delivery. This would increase contact time between the hydrogel and the mucosa while preserving normal ciliary functioning. Following optimization, the final formulation underwent characterization through an examination of the in vitro drug release profile via dialysis under sink conditions. Additionally, homogeneity of its composition was assessed using Raman Confocal Spectroscopy. The results demonstrate complete mixing of drug and polymers within the hydrogel matrix. Furthermore, the formulation exhibits sustained release profile, with 73.76% of the drug being delivered after 5 h in vitro. This will enable future studies to assess the possibility of using this formulation to treat certain mental disorders. We have successfully developed a promising thermosensitive and mucoadhesive hydrogel with a gelling temperature of around 32 °C, a viscosity close to 100 mPas and a mucoadhesion of nearly 4.20 N·m.

Chronic wounds represent a serious worldwide concern, being often associated with bacterial infections. As the prevalence of bacterial infections increase, it is crucial to search for alternatives. Essential oils (EOs) constitute a promising option to antibiotics due to their strong anti-inflammatory, analgesic, antioxidant and antibacterial properties. However, such compounds present high volatility. To address this issue, a drug delivery system composed of coaxial wet-spun fibers was engineered and different EOs, namely clove oil (CO), cinnamon leaf oil (CLO) and tea tree oil (TTO), were loaded. Briefly, a coaxial system composed of two syringe pumps, a coagulation bath of deionized water, a cylindrical-shaped collector and a coaxial spinneret was used. A 10 % w/v polycaprolactone (PCL) solution was combined with the different EOs at 2 × minimum bactericidal concentration (MBC) and loaded to a syringe connected to the inner port, whereas a 10 % w/v cellulose acetate (CA) solution mixed with 10 % w/v polyethylene glycol (PEG) at a ratio of 90:10 % v/v (to increase the fibers\' elasticity) was loaded to the syringe connected to the outer port. This layer was used as a barrier to pace the release of the entrapped EO. The CA\'s inherent porosity in water coagulation baths allowed access to the fiber\'s core. CA was also mixed with 10 % w/v polyethylene glycol (PEG) at a ratio of 90:10 % v/v (CA:PEG), to increase the fibers\' elasticity. Microfibers maintained their structural integrity during 28 days of incubation in physiological-like environments. They also showed high elasticities (maximum elongations at break >300 %) and resistance to rupture in mechanical assessments, reaching mass losses of only ≈ 2.29 % - 57.19 %. The EOs were released from the fibers in a prolonged and sustained fashion, in which ≈ 30 % of EO was released during the 24 h of incubation in physiological-like media, demonstrating great antibacterial effectiveness against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Pseudomonas aeruginosa, the most prevalent bacteria in chronic wounds. Moreover, microfibers showed effective antioxidant effects, presenting up to 59 % of reduction of 2,2-diphenyl-1-picrylhydrazyl (DPPH) activity. Furthermore, the coaxial system was deemed safe for contact with fibroblasts and human keratinocytes, reaching metabolic activities higher than 80 % after 48 h of incubation. Data confirmed the suitability of the engineered system for potential therapeutics of chronic wounds.

Controlled-release drug delivery systems (CRDDS) are more beneficial than conventional immediate release (IRDDS) for reduced intake, prolonged duration of action, lesser adverse effects, higher bioavailability, etc. The preparation of CRDDS is more complex than IRDDS. The hot melt extrusion (HME) technique is used for developing amorphous solid dispersion of poorly water soluble drugs to improve their dissolution rate and oral bioavailability. HME can be employed to develop CRDDS. Sustained release delivery systems (SRDDS), usually given orally, can also be developed using HME. This technique has the advantages of using no organic solvent, converting crystalline drugs to amorphous, improving bioavailability, etc. However, the heat sensitivity of drugs, miscibility between drug-polymer, and the availability of a few polymers are some of the challenges HME faces in developing CRDDS and SRDDS. The selection of a suitable polymer and the optimization of the process with the help of the QbD principle are two important aspects of the successful application of HME. In this review, strategies to prepare SRDDS and CRDDS using HME are discussed with its applications in research.

Ulcerative colitis (UC) is a challenging inflammatory gastrointestinal disorder, whose therapies encounter limitations in overcoming insufficient colonic retention and rapid systemic clearance. In this study, we report an innovative polymeric prodrug nanoformulation for targeted UC treatment through sustained 5-aminosalicylic acid (5-ASA) delivery. Amphiphilic polymer-based 13.5 nm micelles were engineered to incorporate azo-linked 5-ASA prodrug motifs, enabling cleavage via colonic azoreductases. In vitro, micelles exhibited excellent stability under gastric/intestinal conditions while demonstrating controlled 5-ASA release over 24 h in colonic fluids. Orally administered micelles revealed prolonged 24-h retention and a high accumulation within inflamed murine colonic tissue. At an approximately 60% dose reduction from those most advanced recent studies, the platform halted DSS colitis progression and outperformed standard 5-ASA therapy through a 77-97% suppression of inflammatory markers. Histological analysis confirmed intact colon morphology and restored barrier protein expression. This integrated prodrug nanoformulation addresses limitations in colon-targeted UC therapy through localized bioactivation and tailored pharmacokinetics, suggesting the potential of nanotechnology-guided precision delivery to transform disease management.

The advantage of low-temperature forming through direct ink writing (DIW) 3D printing is becoming a strategy for the construction of innovative drug delivery systems (DDSs). Optimization of the complex formulation, including factors such as the printing ink, presence of solvents, and potential low mechanical strength, are challenges during process development. This study presents an application of DIW to fabricate water-soluble, high-dose, and sustained-release DDSs. Utilizing poorly compressible metformin hydrochloride as a model drug, a core-shell delivery system was developed, featuring a core composed of 96 % drug powder and 4 % binder, with a shell structure serving as a drug-release barrier. This design aligns with the sustained-release profile of traditional processes, achieving a 25.8 % reduction in volume and enhanced mechanical strength. The strategy facilitates sustained release of high-dose water-soluble formulations for over 12 h, potentially improving patient compliance by reducing formulation size. Process optimization and multi-batch flexibility were also explored in this study. Our findings provide a valuable reference for the development of innovative DDSs and 3D-printed drugs.

UNASSIGNED: Allergic rhinitis (AR) is an upper airway inflammatory disease of the nasal mucosa. Conventional treatments such as symptomatic pharmacotherapy and allergen-specific immunotherapy have considerable limitations and drawbacks. As an emerging therapy with regenerative potential and immunomodulatory effect, mesenchymal stem cell-derived exosomes (MSC-Exos) have recently been trialed for the treatment of various inflammatory and autoimmune diseases.
UNASSIGNED: In order to achieve sustained and protected release of MSC-Exos for intranasal administration, we fabricated Poly(lactic-co-glycolic acid) (PLGA) micro and nanoparticles-encapsulated MSC-Exos (PLGA-Exos) using mechanical double emulsion for local treatment of AR. Preclinical in vivo imaging, ELISA, qPCR, flow cytometry, immunohistochemical staining, and multiomics sequencing were used for phenotypic and mechanistic evaluation of the therapeutic effect of PLGA-Exos in vitro and in vivo.
UNASSIGNED: The results showed that our PLGA platform could efficiently encapsulate and release the exosomes in a sustained manner. At protein level, PLGA-Exos treatment upregulated IL-2, IL-10 and IFN-γ, and downregulated IL-4, IL-17 and antigen-specific IgE in ovalbumin (OVA)-induced AR mice. At cellular level, exosomes treatment reduced Th2 cells, increased Tregs, and reestablished Th1/Th2 balance. At tissue level, PLGA-Exos significantly attenuated the infiltration of immune cells (e.g., eosinophils and goblet cells) in nasal mucosa. Finally, multiomics analysis discovered several signaling cascades, e.g., peroxisome proliferator-activated receptor (PPAR) pathway and glycolysis pathway, that might mechanistically support the immunomodulatory effect of PLGA-Exos.
UNASSIGNED: For the first time, we present a biomaterial-facilitated local delivery system for stem cell-derived exosomes as a novel and promising strategy for AR treatment.

Boswellia carterii (BC) resins plants have a long historical background as a treatment for inflammation, as indicated by information originating from multiple countries. Twenty-seven diterpenoids have been identified in ethyl acetate and total methanol BC, comprising seventeen boscartins of the cembrane-type diterpenoids and ten boscartols of the prenylaromadendrane-type diterpenoids. Moreover, twenty-one known triterpenoids have also been found, encompassing nine tirucallane-type, six ursane-type, four oleanane-type, and two lupane-type. The cembrane-type diterpenoids hold a significant position in pharmaceutical chemistry and related industries due to their captivating biological characteristics and promising pharmacological potentials. Extraction of BC, creation and assessment of nano sponges loaded with either B. carterii plant extract or DEX, are the subjects of our current investigation. With the use of ultrasound-assisted synthesis, nano sponges were produced. The entrapment efficiency (EE%) of medications in nano sponges was examined using spectrophotometry. Nano sponges were characterized using a number of methods. Within nano sponges, the EE% of medicines varied between 98.52 ± 0.07 and 99.64 ± 1.40%. The nano sponges\' particle sizes varied from 105.9 ± 15.9 to 166.8 ± 26.3 nm. Drugs released from nano sponges using the Korsmeyer-Peppas concept. In respiratory distressed rats, the effects of BC plant extract, DEX salt and their nano formulations (D1, D5, P1 and P1), were tested. Treatment significantly reduced ICAM-1, LTB4, and ILβ 4 levels and improved histopathologic profiles, when compared to the positive control group. Boswellia extract and its nano sponge formulation P1 showed promising therapeutic effects. The effect of P1 may be due to synergism between both the extract and the formulation. This effect was achieved by blocking both ICAM-1 and LTB4 pathways, therefore counteracting the effects of talc powder.