Search Results (1,747)

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. The search for effective, new antineoplastic drugs with fewer side effects for the treatment of CRC continues, with marine-derived compounds emerging as promising candidates. Objectives: This study investigates the anticancer potential of Frondanol, a nutraceutical derived from the Atlantic Sea cucumber Cucumaria frondosa, known for its potent anti-inflammatory properties. Methods: Two human CRC cell lines, Caco-2 and HT-29, were used to test the effects of Frondanol using various in vitro approaches. Results: Frondanol significantly inhibited cell viability in a dose- and time-dependent manner. At a 1:10,000 dilution, viability decreased to around 30% in Caco-2 and 20% in HT-29 after 24 h, dropping to nearly 5% at 48 h. Furthermore, a clonogenic assay showed around 50% reduction in colony formation in both cell lines. Flow cytometry-based Annexin V staining revealed that Frondanol increased early apoptosis to ~5.2% in Caco-2 and ~9.4% in HT-29 cells, while cell cycle analysis showed accumulation of the sub G0 (apoptotic) phase increasing from 1.5% to 14.7% (Caco-2) and from 1.9% to 23.8% (HT-29). At the molecular level, Frondanol treatment significantly decreased anti-apoptotic protein B-cell lymphoma (Bcl)-2 expression while increasing the expression of the proapoptotic protein Bcl-2-associated X-protein. Additionally, Frondanol markedly induced cytochrome c release from the mitochondria and activated caspase-9, caspase-7, and caspase-3 after treatment, alongside cleavage of the caspase-3 substrate poly (ADP-ribose) polymerase. Frondanol inhibited 5-lipoxygenase activity, further contributing to its anticancer effects. Conclusions: In conclusion, Frondanol inhibits CRC cell proliferation and induces apoptosis through the mitochondrial pathway in vitro, suggesting that it is a potential nutraceutical for the prevention of human colorectal cancer or a valuable source of anticancer compounds. Full article

Biodegradable Pickering emulsions are attracting increased appeal owing to their promising and diversifying therapeutic applications. In this study, for the first time, a novel therapeutic Pickering emulsion stabilized with ginger powder (GA4) was formulated, characterized, and tested for doxorubicin (DOX) delivery. GA4_Pes physicochemical characterization by DLS (Dynamic Light Scattering), POM (Polarized Optical Microscopy), Cryo-SEM (Cryo-Scanning Electron Microscopy), TEM (Transmission Electron Microscopy), and rheology testing confirmed stability for at least one month, solid-like gel properties, and multiple morphology even at a low concentration of stabilizer. In addition, the morphological, dimensional, and rheological properties of some GA4_Pe loaded with DOX (GA4_Pe@DOX) were examined. These formulations were of the w/o/w type, stable for at least 28 days, and showed efficient doxorubicin internalization. A 24 h in vitro release assay displayed a sustained and pH-dependent release, with 30% and 50% chemotherapeutic released at pH 7.4 and 5.6, respectively. Furthermore, in vitro cell viability assessment performed using GA4_Pe showed no toxicity on immortalized 3T3 mouse embryonic fibroblasts but a small significant inhibitory effect on human breast cancer cell line MCF7. Interestingly, the GA4_Pe@DOX emulsion exerted a cytotoxic effect on MCF7 cells very similar to that of the free DOX solution with the same doses of DOX loaded in the same emulsion. Therefore, the total biocompatibility/biodegradability, good drug entrapment, and high stability, as well as the prolonged release and anti-tumor efficacy maintenance of the loaded drug, suggest a feasible application of ginger powder-based Pickering emulsions for topical delivery as a selective therapeutic platform in targeted formulations of antineoplastic drugs. Full article

L-asparaginase (L-ASNase) is a vital enzymatic drug widely used for treating acute lymphoblastic leukemia (ALL) and certain lymphomas. However, its clinical application is often limited by a short plasma half-life, pronounced immunogenicity, and systemic toxicities. To address these challenges, we recently developed conjugates of L-ASNase with cationic polymers, enhancing its cytostatic activity by increasing enzyme binding with cancer cells. The present study focuses on the development of liposomal formulations of E. coli L-asparaginase (EcA) and its conjugates with cationic polymers: the natural oligoamine spermine (spm) and a synthetic polyethylenimine–polyethyleneglycol (PEI-PEG) copolymer. This approach aims to improve enzyme encapsulation efficiency and stability within liposomes. Various formulations—including EcA conjugates with polycations incorporated into 100 nm and 400 nm phosphatidylcholine/cardiolipin (PC/CL, 80/20) anionic liposomes—were synthesized as a delivery system of high enzyme load. Fourier Transform Infrared (FTIR) spectroscopy confirmed successful enzyme association with liposomal carriers by identifying characteristic changes in the vibrational bands corresponding to both protein and lipid components. In vitro release studies demonstrated that encapsulating EcA formulations in liposomes more than doubled their half-release time (T_1/2), depending on the formulation. Cytotoxicity assays against Raji lymphoma cells revealed that liposomal formulations, particularly 100 nm EcA-spm liposomes, exhibited markedly superior anti-proliferative activity, reducing cell viability to 4.5%, compared to 35% for free EcA. Confocal Laser Scanning Microscopy (CLSM) provided clear visual and quantitative evidence that enhanced cellular internalization of the enzyme correlates directly with its cytostatic efficacy. Notably, formulations showing higher intracellular uptake produced greater cytotoxic effects, emphasizing that hydrolysis of asparagine inside cancer cells, rather than extracellularly, is critical for therapeutic success. Among all tested formulations, the EcA-spermine liposomal conjugate demonstrated the highest fluorescence intensity within cells providing enhanced cytotoxicity. These results strongly indicate that encapsulating cationically modified L-ASNase in liposomes is a highly promising strategy to improve targeted cellular delivery and prolonged enzymatic activity. This strategy holds significant potential for developing more effective and safer antileukemic therapies. Full article

Background: This study evaluates the impact of fibrinogen enrichment on the structural, mechanical, and bioactive properties of fibrin scaffold derived from balanced protein-concentrate plasma (BPCP), an autologous platelet-rich plasma (PRP) formulation with elevated extraplatelet content. Methods: A novel high-fibrinogen BPCP (HF-BPCP) scaffold was produced by combining BPCP platelet lysate with a concentrated fibrinogen solution at a 1:1 ratio, yielding nearly four-fold physiological fibrinogen levels. Comparative analyses between HF-BPCP and standard BPCP included platelet and fibrinogen quantification, scanning electron microscopy (SEM), rheology, indentation, adhesion testing, coagulation kinetics, retraction assays, biodegradation profiling, and growth factor (GF) release kinetics. Results: HF-BPCP displayed significantly denser fibrin networks with thinner fibers, higher porosity, and markedly faster coagulation times compared to BPCP. Mechanically, HF-BPCP exhibited greater stiffness, higher energy dissipation, and more stable adhesion, while almost eliminating scaffold retraction at 24 h. Despite improved early handling and structural integrity, HF-BPCP degraded more rapidly in vitro under tissue plasminogen activator exposure. GF release analysis showed reduced early peaks of platelet-derived factors (TGF-β1, PDGF-AB, VEGF) but sustained release thereafter, while extraplatelet factors (IGF-1, HGF) exhibited similar profiles between scaffolds. Conclusions: These results indicate that fibrinogen enrichment synergizes with the elevated extraplatelet protein profile of BPCP to enhance scaffold mechanical stability, handling properties, and controlled GF delivery. HF-BPCP combines the adhesive, structural, and bioactive features of fibrin sealants with the regenerative potential of PRP, offering a fully autologous alternative for clinical applications requiring rapid coagulation, high mechanical support, and sustained GF availability. Further preclinical and clinical studies are needed to evaluate therapeutic efficacy in the regenerative medicine field. Full article

This study emphasizes overcoming the challenges of targeted drug delivery in colon cancer therapy by developing gastrointestinal (GI) stable, pectin-coated nanoliposomes for the oral delivery of Apigenin-Cyclodextrin Complex as an in situ gel formation. Initially, the formulation was strategically designed using design expert software for formulation optimization. FTIR and XRD studies were conducted to ensure physical compatibility and to confirm the encapsulation of apigenin within the formulation. In process optimization, among all seventeen formulations run tested, PNL (Api-Cy)-13 was identified for the highest drug loading, favourable size dimension of particle with zeta potential, and spherical external morphology through SEM analysis. The metered drug release during an in vitro study for PNL (Api-Cy)-13 was remarkably high (more than 75% of drug availability in the colonic environment, precisely in contrast to only 20% in the gastric phase in a sustained release manner), focused on colon drug targeting as an in situ gel. Furthermore, apigenin release from PNL (Api-Cy)-13 in an ex vivo chick ileum permeability study was observed both in the absence and presence of 1% vancomycin. An incremental apigenin release in the absence of the antibiotic (1% vancomycin) indicated gut microbial-associated and pectinase-mediated drug release. Here, pectin degradation materializes by the colonic microbial environment, which facilitates desirable incremental colonic drug permeation. Finally, an in vitro MTT assay and a competitive flowcytometric cell uptake study with PNL (Api-Cy)-13 using HCT-116 cells proved significant superiority in cytotoxicity profile for apigenin when delivered as an optimized coated nanoliposome in comparison to free apigenin or other non-modified nano-formulation. Also, the inhibition of the cell efflux process was validated by Multidrug Resistance 1 (MDR1) gene regulation. These observations establish an undoubted promise for the novel biopolymer, pectin-based apigenin-cyclodextrin nanoliposomes as targeted therapy in colon cancer with significant in vivo pharmacokinetics and safety profile. Full article

This study aimed to assess the biocompatibility and bioactivity of three different silver nanoparticles (AgNPs) and calcium hydroxide [Ca(OH)₂] mixtures against human dental pulp stem cells (hDPSCs). hDPSCs were treated with one of the following medicaments: 2 nm mixture, 5 nm mixture, 10 nm mixture, Ca(OH)₂ alone, and triple antibiotic paste (TAP). Cell viability was evaluated using the Cell Counting Kit-8 and LIVE/DEAD Viability/Cytotoxicity Kit. Reactive oxygen species (ROS) were quantified using the 2′,7′-dichlorofluorescein diacetate redox probe. Transforming growth factor (TGF)-β1, interleukin (IL)-1β, tumor necrosis factor (TNF)-α>, and alkaline phosphatase (ALP) were quantified using enzyme-linked immunosorbent assays. Mineralization was assessed using Alizarin Red S staining. Data were compared across groups using the Kruskal–Wallis test and within groups using the Wilcoxon signed-rank test (p < 0.05). Ca(OH)₂ alone and the 10 nm mixture demonstrated the highest cell viability and lowest ROS release (p < 0.05), while the 2 nm and 5 nm mixtures resulted in decreased viability and significant morphological distortion of the cells. Ca(OH)₂ alone and the 10 nm mixture comparably demonstrated the highest production of anti-inflammatory cytokine TGF-β1 (p < 0.05), the lowest production of proinflammatory cytokines IL-1β and TNF-α (p < 0.05), and the highest ALP release and mineralization (p < 0.05). Within the limitations of this in vitro study, Ca(OH)₂ alone and the 10 nm mixture improved hDPSCs’ viability, proliferation, differentiation, and mineralization. Both illustrated a significantly higher anti-inflammatory response by the residing stem cell population. Full article

Purple waxy corn cobs (PWCCs) represent an underutilized agricultural waste rich in anthocyanins with promising cosmeceutical potential. This study investigated niosome-based encapsulation to enhance the stability and bioactivity of PWCC anthocyanin extracts. PWCC extract was macerated in 50% ethanol. The extract exhibited a high total anthocyanin content (3.02 ± 0.81 mg C3GE/L), while cyanidin-3-glucoside identified as the major anthocyanin (1.17 ± 0.02 mg/g dry weight). Furthermore, the extracts showed strong antioxidant activities as evidence by DPPH, ABTS, and FRAP assays. The optimized niosome preparations synthesized by the probe sonication method exhibited better entrapment efficiency (80–85%), nanoscale particle size (185–296 nm), and stable zeta potential (−29 to −32 mV). TEM verification of the spherical morphology and FT-IR spectra confirmed the successful loading of anthocyanins. The thermal stability test exhibited negligible changes in the particle size and zeta potential. Furthermore, in vitro release profile followed the Higuchi model, indicating enhanced release kinetics. Biological assays demonstrated moderate UVB protection effects and potent anti-melanogenesis activity in B16F10 cells. Notably, formulation N5 exhibited the highest tyrosinase inhibition and melanin synthesis suppression. These findings indicate that niosome-based encapsulation represents a promising strategy for enhancing the stability, bioavailability, and biological efficacy of anthocyanin extracts, especially in the cosmetic and pharmaceutical industries. Full article

Background/Objectives: Children with autism spectrum disorder (ASD) frequently experience poor compliance with oral medication due to bitterness, unpleasant taste, and unsuitable dosage forms such as large tablets or capsules. Risperidone, a widely prescribed antipsychotic for managing ASD symptoms, is particularly challenging in this regard. The present study aimed to develop a novel sucrose-based microfiber drug delivery system to improve the palatability, acceptance, and bioavailability of risperidone in pediatric patients with ASD. Methods: Risperidone was incorporated into sucrose microfibers using centrifugal spinning technology. Fiber morphology was characterized by scanning electron microscopy (SEM). Drug loading (DL), encapsulation efficiency (EE%), and disintegration time were measured. In vitro drug release and cytotoxicity assays were performed using human foreskin fibroblast cells (HFF-1). An in vivo palatability and preference study was conducted in male BALB/c mice to evaluate the acceptability of the formulation compared with a commercial risperidone oral solution. Results: SEM analysis revealed smooth, bead-free, non-porous fibers with uniform morphology and size distribution. The formulation showed a rapid disintegration time of ~3 s, DL of 30 ± 5 µg/mg, and EE% of 60 ± 10%. Approximately 50% of risperidone was released within 15 min. Cytotoxicity testing confirmed that concentrations ≤ 125 µg/mL maintained high cell metabolic activity, indicating biocompatibility. In vivo, the microfiber solution demonstrated a strong preference (93%) compared with the commercial oral solution (30%). Conclusions: Risperidone-loaded sucrose microfibers represent a promising fast-dissolving oral delivery system for children with ASD. This child-friendly formulation improves palatability and compliance while maintaining safety and drug release performance. Full article

Background/Objectives: Primary dysmenorrhea is a prevalent condition that causes severe uterine cramps in women worldwide. The objective of this work was to synthesize and characterize a novel immediate-release system using vitexin and ZIF-8, and to evaluate its pharmacological action in a model of primary dysmenorrhea. Methods: A 2² full factorial design guided the synthesis of the system. Physicochemical characterization was performed by FT-IR, TG, DSC, SEM, XRD, and in vitro release tests. Pharmacological activity was assessed in an oxytocin-induced dysmenorrhea model in mice. In addition, in silico molecular docking and molecular dynamics simulations were conducted to explore the potential mechanism of action of vitexin. Results: Optimal yield and loading capacity were achieved at the high levels of the factorial design. Characterization analyses confirmed the successful formation of the vitexin@ZIF-8 (VIT@ZIF-8) system. The release study demonstrated a markedly enhanced dissolution rate of vitexin. Both isolated vitexin and VIT@ZIF-8 reduced abdominal writhing when administered orally at 3 and 30 mg/kg, while intraperitoneal activity was observed only at 30 mg/kg. Computational analyses revealed favorable interactions of vitexin with aldose reductase (AKR1C3), suggesting this enzyme as a potential molecular target in dysmenorrhea. Conclusions: The VIT@ZIF-8 system represents a promising strategy to improve the dissolution profile of vitexin, although pharmacological activity in this model was not superior to the isolated compound. The combined in vivo and in silico evidence supports vitexin as a potential antidysmenorrheic agent, possibly through modulation of AKR1C3. These findings open avenues for future studies addressing the molecular pathways of vitexin and for the development of novel therapeutic approaches for primary dysmenorrhea. Full article

Abdominal aortic aneurysm (AAA) is a dilatation of the distal aorta to a diameter of 50% or more of its normal size of about 2 cm. Risk of aortic rupture can be nearly eliminated with either open surgery or endovascular repair. Procedural risks limit the value of these interventions unless the diameter of the aneurysm has reached a critical threshold (established as 5.5 cm in men or 5.0 cm in women). Thus, patients are monitored until this threshold is reached. Approximately 80% of small AAA will grow and exceed the threshold, providing a therapeutic window for altering this natural history and reducing the risk of rupture. Previous work in our lab has utilized adipose-derived mesenchymal stem cells (ASCs) to treat AAA in vivo, preserving elastic fibers and slowing aneurysm expansion. This work sought to create a delivery system for therapeutic extracellular vesicles (ASC-EVs) secreted by ASCs. Our delivery system incorporated the biocompatibility of regenerated silk fibroin (RSF), the magnetic moveability of iron oxide nanoparticles (IONPs), and the regenerative nature of ASC-EVs to create silk-iron packaged extracellular vesicles (SIPEs). Using this system, we tested the ability to magnetically localize the SIPEs and release their encapsulated ASC-EVs to exert their regenerative effects in vitro. We were successful in magnetically localizing the SIPEs in vitro and silk-iron microparticles (SIMPs) in vivo and in detecting their releasates via flow cytometry and cellular uptake assays. However, while their releasates were detected, their biological effects were diminished compared to unencapsulated controls. Thus, additional optimization related to loading efficiency is needed. Full article

Primary hip and knee arthroplasties are common surgeries in the U.S., with periprosthetic joint infection (PJI) being the leading cause of implant revision. Systemic antibiotics often fail to achieve sufficient local concentrations, driving interest in localized drug delivery. Titanium (Ti) implants modified with titania nanotubes (TNTs) provide an increased surface area for drug loading and controlled release. Previous studies have shown that gentamicin-loaded TNTs inhibit Staphylococcus aureus growth in vitro without compromising osteoblast viability. This study investigated the effect of gentamicin–chitosan (GC)-coated TNT implants in a murine model, hypothesizing a positive impact on osseointegration. Titanium alloy (Ti6Al4V) wires were anodized to form TNTs and then coated with gentamicin–chitosan (GC) via electrophoretic deposition. Implants (Bare, TNT, TNT+GC; n = 30) were inserted bilaterally into femoral canals of C57BL/6J mice. After > 1 month, osseointegration was assessed by histological point counting, scanning electron microscopy (SEM)-based areal analysis, and mechanical pull-out testing. ANOVA was used to identify differences between groups, and linear regression was applied to account for harvest time, bone contact area, and anatomical section. Bone area fraction (BAF) around the implant measured by the SEM–areal method was significantly higher around TNT+GC (18.4% ± 1.1) and TNT (16.5% ± 1.4) versus Bare (9.0% ± 2.3) (p < 0.0028) implants. The maximum fixation strength was higher for TNT (0.878 ± 0.175 N/mm²) and TNT+GC (0.853 ± 0.215N/mm²) when compared to bare implants 0.316 ± 0.082 N/mm²) (p = 0.048 and p = 0.050, respectively). No significant differences appeared between TNT and TNT+GC. These findings indicate that GC coatings on TNT implants do not impair osseointegration and may even enhance bone–implant integration. Such coatings may therefore provide dual benefits, offering antibacterial protection while improving bone fixation, making them a promising strategy for PJI prevention. Further long-term studies are needed to confirm durability and clinical translation. Full article

Background: Mango seed kernels, an agro-industrial waste byproduct, constitute approximately 40–50% of the fruit’s weight and serve as a substantial source of starch. There are only a few reported studies on the pharmaceutical applications of Mango Seed Kernel Starch (MSKS) and drug carriers produced from this source. This study aims to isolate starch from mango seed kernels (MSKS), prepare drug-loaded mango seed kernel starch nanoparticles (MSKSNPs), and study the in vitro transdermal permeation. Methods: The MSKS was prepared using the alkaline method and freeze-dried. The prepared starch was analyzed for physicochemical properties relative to corn starch. The mango seed kernel starch nanoparticles (MSKSNPs) were prepared using mild alkali hydrolysis and the ultrasonication method. The model drug selected for this study was diclofenac sodium (DS), a commonly prescribed non-steroidal anti-inflammatory drug. Results: The average particle size of the drug-loaded nanoparticles was 140.0 ± 3.6 nm, with a PDI of 0.42 ± 0.03. The Transmission Electron Microscopy images confirmed the globular structure of MSKSNPs. X-ray Diffraction revealed that the diclofenac crystal size decreased to 14 nm from 33 nm in the pure drug, confirming the amorphous nature of MSKSNPs. The drug-loaded MSKSNPs showed a % encapsulation efficiency of 92.4 ± 3.7 and % drug loading of 31.08 ± 0.96. The cumulative drug released from MSKSNPs after 6 h, 12 h, and 24 h was found to be 25.58 ± 1.30, 59.68 ± 2.98, and 127.5 ± 6.4 μg/cm^2, respectively, which was more than the ethanolic drug solution with statistical significance (p-value < 0.01) along with enhanced skin retention. Conclusions: MSKSNPs were efficiently synthesized using mild alkali hydrolysis and ultrasonication, showing enhanced transdermal delivery. Skin retention was significantly higher in MSKSNPs (p-value < 0.05). The cytotoxic studies revealed that both formulations exhibit similar dose-dependent cytotoxicity, with no significant difference (p > 0.05) in their potency under the tested conditions. Full article

Background/Objectives: Lidocaine hydrochloride (LD-HCl) is the most commonly used local anesthetic in dentistry, often administered with epinephrine to extend its duration and reduce systemic absorption. However, its relatively short duration of action, the need for repeated injections, and the unpleasant taste may limit patient compliance and procedural efficiency. This study aimed to develop and evaluate a novel injectable nanoemulsion-based in situ gel depot system of LD to provide prolonged anesthetic activity. Methods: LD-loaded nanoemulsions were formulated by high-shear homogenization followed by probe sonication, employing Miglyol 812 N (oil phase), a combination of Tween 80 and soy lecithin (surfactant–co-surfactant), glycerin, and deionized water (aqueous phase). The selected nanoemulsion (S1) was dispersed in a thermoreversible poloxamer solution to form a nanoemulgel. The preparation was evaluated for globule diameter and uniformity, zeta potential, surface morphology, pH, drug content, stability, rheological behavior, injectability, and in vitro drug release. Analgesic efficacy was assessed via tail-flick and thermal paw withdrawal latency tests in Wistar rats. Cardiovascular safety was monitored using non-invasive electrocardiography and blood pressure measurements. Results: The developed nanoemulsions demonstrated a spherical shape, nanometer size (206 nm), high zeta-potential (−66.67 mV) and uniform size distribution, with a polydispersity index of approximately 0.40, while the nanoemulgel demonstrated appropriate thixotropic properties for parenteral administration. In vitro release profiles showed steady LD release (5 h), following the Higuchi model. In vivo studies showed significantly prolonged analgesic effects lasting up to 150 min (2.5 h) compared to standard LD-HCl injection (p < 0.001), with no adverse cardiovascular effects observed. Conclusions: The developed injectable LD in situ nanoemulgel offers a promising, patient-friendly alternative for prolonged anesthetic delivery in dental and operative procedures, potentially reducing the need for repeated injections and enhancing procedural comfort. Full article

Background: Glucocorticoids are an important class of therapeutics used in a variety of applications, including allotransplantations. Dexamethasone (Dexa) is well-known for its strong anti-inflammatory, immunosuppressive, and anticancer properties. However, its clinical use is often limited by its poor water solubility, poor pharmacokinetics, and high likelihood of systemic side effects. Methods: To address the issues, we tested a combined strategy where our original Drug-Integrating Amphiphilic Nano-Assemblies (DIANAs), a class of self-assembling polymeric nanoparticles designed for controlled drug release, were used to solubilize and deliver dexamethasone palmitate (DexP), a hydrophobic prodrug of dexamethasone. Results: The palmitate chains of the prodrug can form strong van der Waals interactions with the hydrophobic moieties of the PEG-PPS block copolymer used here. In water, this resulted in the self-assembling of stable dexamethasone palmitate–PEG–PPS nanomicelles, termed DexP-nMICs, with a 25 nm average diameter that slowly released Dexa over more than two weeks. Conclusions: Here we demonstrated that DexP-nMICs can carry elevated amounts of Dexa—increasing its solubility in water—prolong circulation in its pharmacologically active form in vivo and provide passive targeting to inflammation sites. The anti-inflammatory efficacy of DexP-nMICs was first confirmed in vitro on stimulated macrophages, demonstrating a significant reduction in cytokine secretion. An allogeneic mouse skin transplant model, used to assess the therapeutic potential of DexP-nMICs in vivo, confirmed its ability to provide graft-targeted delivery and prolong graft survival as compared to the unformulated parent drug. Therefore, DexP-nMICs are a promising candidate for sustained and localized use of anti-inflammatory drugs in cell and tissue transplantations. Full article

Tacrolimus is frequently used in immunosuppressive therapy in renal transplant patients and is characterized by high toxicity, a low therapeutic index, and great individual variability. For these reasons, correct dosing is important to ensure patient safety by reducing the incidence of adverse effects while maintaining an optimal blood level that prevents graft loss. New-onset diabetes after transplantation (NODAT) affects 15–30% of patients treated with tacrolimus, with potential differences between immediate-release (IR) and extended-release (ER) formulations. Objective: This study seeks to compare the incidence of NODAT between IR tacrolimus and ER tacrolimus formulations in renal transplant patients and correlate it with in vitro release characteristics. Methods: This is a retrospective pilot study including 66 renal transplant patients (33 IR tacrolimus, 33 ER tacrolimus) followed for 5 years. NODAT was defined according to standard criteria. In vitro dissolution testing was performed at pH values of 1.2, 4.5, and 6.8, with sampling at 15, 30, 60, 90, 120, and 360 min. Results: The obtained results do not indicate differences regarding the incidence of diabetes mellitus in patients treated with the two forms of tacrolimus. The determined NODAT incidence was 42.4% (ER tacrolimus) vs. 39.4% (IR tacrolimus), p = 0.802, and ER tacrolimus showed slower release without significant pH-dependent variations. Conclusions: No significant differences in NODAT incidence were identified between formulations. The release–clinical outcome correlation requires validation in larger multicenter studies. These results contribute to the evidence base for tacrolimus formulation selection in renal transplant patients and other associated pathologies. Full article