Biological Environment Research Articles

Influence of manufacturing parameters on bioactive glass 45S5: Structural analysis and applications in bone tissue engineering

Bioactive glass (BG-45S5) production through the melting process is affected by a wide variety of parameters. This study investigated the synthesis of BG-45S5 granules and the process variables to produce a bioactive and osteoinductive BG for bone grafting applications. The melting process was initially analyzed by varying parameters such as crucible type and pouring environment using P2O5 as phosphorus precursor. The obtained products were characterized by crystalline phases, characteristic chemical groups, particle size distribution, and chemical composition. Materials poured into graphite or steel molds resulted in particle sizes more suitable for applications in granular form. Using a platinum crucible yielded a chemical composition closer to the target when compared with another ceramic crucible. Subsequently, the melting process was evaluated to different phosphorus precursor (P2O5 or Na2HPO4) and melting duration (1 or 2 h) in a platinum crucible verifying their effects on the thermal behavior, chemical composition and structure of BG-45S5. Employing Na2HPO4 as a precursor led to higher glass transition and crystallization temperatures as compared to P2O5, enhancing glass homogeneity and structural stability. The product with better characteristics in terms of composition and structure was further characterized for bioactivity and cell culture behavior, showing a greater amount of mineralization nodules when compared to commercial hydroxyapatite. This is particularly due to its behavior as the solubility and interaction in biological environments.

Poria cocos-derived carbon dots for parallel detection of Cr6+/Fe3+ in complex environments with superior sensitivity

Multifunctional sensor capable of parallel sensing is of great importance thanks to their wide applications and great practicality. In this report, Poria cocos-derived carbon dots (CDs) were adopted for the development of multifunctional sensor for the parallel detection of Cr6+ and Fe3+ with superior sensitivity and applicability. Specifically, extremely low limit of detection (LOD) of 1.07 × 10−3 nM and 1.98 × 10−3 nM were achieved for Cr6+ and Fe3+, respectively. Systematic mechanism explorations revealed that the highly sensitive detection of Cr6+ was attributed to an efficient inner filtering effect (IFE), while the sensing of Fe3+ was realized due to a strong static quenching process. Furthermore, the assay was found to be extremely versatile, achieving the reliable detection of Cr6+ and Fe3+ in multiple natural water environments and even biological environment. Utilizing the different reactions of Cr6+ and Fe3+ towards masking reagents, a logic gate that could effectively eliminate the mutual interference of Cr6+ and Fe3+ was successfully designed.

Bioprinting of Cells, Organoids and Organs-on-a-Chip Together with Hydrogels Improves Structural and Mechanical Cues.

The 3D bioprinting technique has made enormous progress in tissue engineering, regenerative medicine and research into diseases such as cancer. Apart from individual cells, a collection of cells, such as organoids, can be printed in combination with various hydrogels. It can be hypothesized that 3D bioprinting will even become a promising tool for mechanobiological analyses of cells, organoids and their matrix environments in highly defined and precisely structured 3D environments, in which the mechanical properties of the cell environment can be individually adjusted. Mechanical obstacles or bead markers can be integrated into bioprinted samples to analyze mechanical deformations and forces within these bioprinted constructs, such as 3D organoids, and to perform biophysical analysis in complex 3D systems, which are still not standard techniques. The review highlights the advances of 3D and 4D printing technologies in integrating mechanobiological cues so that the next step will be a detailed analysis of key future biophysical research directions in organoid generation for the development of disease model systems, tissue regeneration and drug testing from a biophysical perspective. Finally, the review highlights the combination of bioprinted hydrogels, such as pure natural or synthetic hydrogels and mixtures, with organoids, organoid-cell co-cultures, organ-on-a-chip systems and organoid-organ-on-a chip combinations and introduces the use of assembloids to determine the mutual interactions of different cell types and cell-matrix interferences in specific biological and mechanical environments.

Distinguishing Protein Corona from Nanoparticle Aggregate Formation in Complex Biological Media Using X-ray Photon Correlation Spectroscopy.

In biological systems, nanoparticles interact with biomolecules, which may undergo protein corona formation that can result in noncontrolled aggregation. Therefore, comprehending the behavior and evolution of nanoparticles in the presence of biological fluids is paramount in nanomedicine. However, traditional lab-based colloid methods characterize diluted suspensions in low-complexity media, which hinders in-depth studies in complex biological environments. Here, we apply X-ray photon correlation spectroscopy (XPCS) to investigate silica nanoparticles (SiO2) in various environments, ranging from low to high complex biological media. Interestingly, SiO2 revealed Brownian motion behavior, irrespective of the complexity of the chosen media. Moreover, the SiO2 surface and media composition were tailored to underline the differences between a corona-free system from protein corona and aggregates formation. Our results highlighted XPCS potential for real-time nanoparticle analysis in biological media, surpassing the limitations of conventional techniques and offering deeper insights into colloidal behavior in complex environments.

Optimization of highly sensitive three-layer photonic crystal fiber sensor based on plasmonic

In this work, a photonic crystal fiber (PCF) refractive index (RI) sensor has been designed and optimized. The RIs range covered by the sensor is from 1.38 to 1.41. The proposed optical sensor has three layers of air holes with 24, 12 and 6 holes in each layer. The geometry parameters of the proposed sensor (the radius of the air holes and the thickness of the plasmonic layer) have been optimized using the Nelder-Mead algorithm and the FEM numerical with the objective of achieving the highest sensitivity. To achieve an optimized structure with minimal sensitivity to fabrication errors, the rotation angle of the hole layers has been analyzed. The results indicate that, due to the specific geometry of the proposed structure, variations in the rotation angle and displacement of the air holes have no significant impact on the outcomes. The results also indicate that the sensor’s maximum amplitude sensitivity (AS), maximum wavelength sensitivity (WS), and figure of merit (FOM) are 10000 (RIU−1), 23000 (nm/RIU) and 131 (RIU−1) respectively. The optimized design provides high sensitivity, a wide diagnostic range for the detection of the analytes’ RIs, and the advantages of a gold plasmonic layer, ensuring high stability in biological environments. This combination results in enhanced performance of the sensor for various applications particularly in biosensing and medical fields. The designed structural geometry also eliminates the effects of tolerances in manufacturing processes which makes the proposed PCF device a very efficient sensor.

Tailored Metal-Based Catalysts: A New Platform for Targeted Anticancer Therapies.

Innovative strategies for targeted anticancer therapies have gained significant momentum, with metal complexes emerging as tunable catalysts for more effective and safer treatments. Rational design and engineering of metal complexes enable the development of tailored molecular structures optimized for precision oncology. The strategic incorporation of metal complex catalysts within combinatorial therapies amplifies their anticancer properties. This perspective highlights the advancements in synthetic strategies and rational design since 2019, showing how tailored metal catalysts are optimized by designing structures to release or in situ synthesize active drugs, leveraging the target-specific characteristics to develop more precise cancer therapies. This review explores metal-based catalysts, including those conjugated with biomolecules, nanostructures, and metal-organic frameworks (MOFs), highlighting their catalytic activity in biological environments and their in vitro/in vivo performance. To sum up, the potential of metal complexes as catalysts to reshape the landscape of anticancer therapies and foster novel avenues for therapeutic advancement is emphasized.

Exploring the therapeutic potential of lipid-based nanoparticles in the management of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a highly malignant and invasive tumor with significant mortality and morbidity. Current treatment modalities such as surgery, radiotherapy, and chemotherapy encounter significant limitations, such as poor targeting, systemic toxicity, and drug resistance. There is an urgent need for novel therapeutic strategies that offer targeted delivery, enhanced efficacy, and reduced side effects. The advent of lipid-based nanoparticles (LNPs) offers a promising tool for OSCC therapy, potentially overcoming the limitations of current therapeutic approaches. LNPs are composed of biodegradable and biocompatible lipids, which minimize the risk of toxicity and adverse effects. LNPs can encapsulate hydrophobic drugs, improving their solubility and stability in the biological environment, thereby enhancing their bioavailability. LNPs demonstrate significantly higher ability to encapsulate lipophilic drugs than other nanoparticle types. LNPs offer excellent storage stability, minimal drug leakage, and controlled drug release, making them highly effective nanoplatforms for the delivery of chemotherapeutic agents. Additionally, LNPs can be modified by complexing them with specific target ligands on their surface. This surface modification allows the active targeting of LNPs to the tumors in addition to the passive targeting mechanism. Furthermore, the PEGylation of LNPs improves their hydrophilicity and enhances their biological half-life by reducing clearance by the reticuloendothelial system. This review aims to discuss current treatment approaches and their limitations, as well as recent advancements in LNPs for better management of OSCC.

A dual-channel fluorescent probe for differential detection of HClO and N2H4

Hypochlorous acid (HClO) and hydrazine (N2H4) are both toxic to the biological environment. The development of a fluorescent probe capable of achieving accurate and sensitive detection of HClO and N2H4 in both organisms and environmental systems is essential to reveal their various physiological and pathological functions. For this work, a dual-channel fluorescent probe PI was developed, which achieved different fluorescence signals in blue and green channels in response to HClO and N2H4 by adjusting the donor and receptor before and after the reaction of fluorophore. PI has the advantages of quick response (12 min for HClO, 15 min for N2H4), good selectivity and high sensitivity for the recognition of HClO and N2H4 in solutions. The probe PI showed good linearity for HClO in the concentration range of 15–50 μM with a limit of detection of 41 nM. It also showed good linearity for N2H4 in the concentration range of 0–200 μM with a limit of detection of 23 nM for N2H4. Furthermore, probe PI was utilized to detect HClO and N2H4 in cells, zebrafish and Arabidopsis thaliana seedlings. The results demonstrate that the probe PI is a promising tool for monitoring HClO and N2H4 in biological systems and the environment.

Mutual Relationships of Nanoconfined Hexoses: Impacts on Hydrodynamic Radius and Anomeric Ratios.

Although all hexose sugars share the same chemical formula, C6H12O6, subtle differences in their stereochemical structures lead to their various biological roles. Due to their prominent role in metabolism, hexose sugars are commonly found in nanoconfined environments. The complexity of authentic nanoconfined biological environments makes it challenging to study how confinement affects their behavior. Here, we present a study using a common model system, AOT reverse micelles, to study hexose sugars in nanoconfinement. We examine how reverse micelles affect the hexoses, how the hexoses affect reverse micelle formation, and the differences between specific hexoses: glucose, mannose, and galactose. We find that addition of glucose, mannose or galactose to reverse micelles that already contain water leaves their size smaller or nearly unchanged. Introducing aqueous hexose solution yields reverse micelles smaller than those prepared with the same volume of water. We use 1H NMR to show how the nanoconfined environment impacts hexose sugars' anomeric ratios. Nanoconfined mannose and galactose display smaller changes in their anomeric ratios compared to glucose. These conclusions may provide insights about the biological roles of each hexose when studied under a more authentic nanoconfined system.

A non-enzymatic hydrogen peroxide biosensor based on cerium metal-organic frameworks, hemin, and graphene oxide composite

This study presents the development of a novel non-enzymatic electrochemical biosensor for the real-time detection of hydrogen peroxide (H2O2) based on a composite of cerium metal–organic frameworks (Ce-MOFs), hemin, and graphene oxide (GO). The Ce-MOFs served as an efficient matrix for hemin encapsulation, while GO enhanced the conductivity of the composite. Characterization techniques including scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy, UV–vis spectroscopy, and thermogravimetric analysis (TGA) confirmed the successful integration of hemin into the Ce-MOFs. The Ce-MOFs@hemin/GO-modified sensor demonstrated sensitive H2O2 detection due to the exceptional electrocatalytic activity of Ce-MOFs@hemin and the high conductivity of GO. This biosensor exhibited a linear response to H2O2 concentrations from 0.05 to 10 mM with a limit of detection (LOD) of 9.3 μM. The capability of the biosensor to detect H2O2 released from human prostate carcinoma cells was demonstrated, highlighting its potential for real-time monitoring of cellular oxidative stress in complex biological environments. To further assess its practical applicability, the sensor was tested in human serum samples, yielding promising results with recovery values ranging from 94.50 % to 103.29 %. In addition, the sensor showed excellent selectivity against common interfering compounds due to the outstanding peroxidase-like activity of the composite.

Prospective study on functional outcome of distal femur fracture treated by open reduction and internal fixation using distal femur locking plate in Tibebe Ghion Specialized Hospital, Bahirdar, North West Ethiopia

BackgroundDistal femur fractures account for 6% of femur fractures. The treatment of distal femur fractures is challenging. Historically, nonoperative management has been the mainstay of management, which has evolved to operative management. There is no single implant used for all types of distal femur fractures. The implant evolves with time. The introduction of a distal femur locking plate (DF LCP) has had a great impact on the treatment. In developing countries like Ethiopia, there is scarcity of studies on functional outcome of operative treatment. So, this study aimed to assess the functional outcome of distal femur fractures treatment using distal femur locking plate.MethodsThis prospective cohort study was carried out among adult patients with distal femur fractures treated using distal femur locking plate at Tibebe Ghion Specialized Hospital from august 2022 to July 2023. A total of 60 patients with AO Type A and Type C fracture were included. All patients were followed for 6 months. Functional outcomes were assessed using Neer’s scoring system. Data was entered and analyzed using SPSS 27. Frequency, mean and cross tabulation were used to summarize descriptive statistics. Multinomial logistic regression was used to test the associations.ResultsIn our study out of 60 patients ,48.3% (29) had excellent functional outcomes, 30% (18) had good functional outcomes, 10% (6) had fair functional outcomes and 11.7% (7) had unsatisfactory functional outcomes according to Neer’s scoring system. Patients with closed distal femur fractures had 5 times higher probability of excellent functional outcome than those patients with open distal femur fractures (AOR (2.49(5.8 ,1.07)). Patients who had regular follow up had 7 times higher probability of excellent functional outcome than those who had no regular follow up (AOR 7.16(1.11,46.22)). The average union period was 4.63 months, with only 2 patients experiencing delayed union.ConclusionClosed fracture and regular follow up were determining factors for better functional outcomes. Closed fractures preserve the biological environment, which facilitates early fracture healing. The regular follow up helped patients to assess their rehabilitation status and pick any complication early.

Improved thermometry via luminescence lifetime ratio of Er3+ and Tm3+ operated in the biological window

The luminescent intensity ratio of Lanthanide-doped nanocrystals has been widely used for non-contact thermometry but is still facing difficulties in biological applications due to spectrum distortion caused by tissues. Lifetime-based thermometry is the best alternative to other typical thermometry methods. However, its main drawback is the limited sensitivity. This paper introduces an innovative method known as luminescence lifetime ratio, which enhances luminescence thermometry by combining two emission bands with opposite decay behaviors with temperature. As a proof of concept, a core-shell structure separately containing Tm3+ and Er3+ was synthesized and exhibited two strong emission bands centered at 800 nm and 1530 nm, which are located in the NIR-I and NIR-III biological windows. The commonly used LIR thermometer, an Er/Yb co-doped NaYF4 sample, was also synthesized for comparison. By using chicken tissues of varying thicknesses (1 mm and 3 mm), it was revealed that the deep-tissue penetration and accuracy in biological environments of luminescence lifetime ratio are evidently improved than the widely-used technique of luminescence intensity ratio, although the relative sensitivity of is not much better. In summary, the luminescence lifetime ratio technique enables novel and more accurate temperature sensing within the wavelength range that is suitable for biological applications.

3D Bioprinting Using Universal Fugitive Network Bioinks.

Three-dimensional (3D) bioprinting has emerged with potential for creating functional 3D tissues with customized geometries. However, the limited availability of bioinks capable of printing 3D structures with both high-shape fidelity and desired biological environments for encapsulated cells remains a key challenge. Here, we present a 3D bioprinting approach that uses universal fugitive network bioinks prepared by loading cells and hydrogel precursors (bioink base materials) into a 3D printable fugitive carrier. This approach constructs 3D structures of cell-encapsulated hydrogels by printing 3D structures using fugitive network bioinks, followed by cross-linking printed structures and removing the carrier from them. The use of the fugitive carrier decouples the 3D printability of bioinks from the material properties of bioink base materials, making this approach readily applicable to a range of hydrogel systems. The decoupling also enables the design of bioinks for the biological functionality of the final printed constructs without compromising the 3D printability. We demonstrate the generalizable 3D printability by printing self-supporting 3D structures of various hydrogels, including conventionally non-3D printable hydrogels and those with a low polymer content. We conduct preprinting screening of bioink base materials through 3D cell culture to select bioinks with high cell compatibility. The selected bioinks produce 3D constructs of cell-encapsulated hydrogels with both high-shape fidelity and high cell viability and proliferation. The universal fugitive network bioink platform could significantly expand 3D printable bioinks with customizable biological functionalities and the adoption of 3D bioprinting in diverse research and applied settings.

Spirocyclic pyrrolidinyl nitroxides with exo-methylene substituents.

Nitroxides are stable organic radicals with exceptionally long lifetimes, which render them uniquely suitable as observable probes or polarising agents for spectroscopic investigation of biomolecular structure and dynamics. Radical-based probes for biological applications are ideally characterized by both robustness towards reductive degradation and beneficial electron spin relaxation parameters. These properties are largely influenced by the molecular structure of the nitroxide scaffold, and also by the conformations it prefers to adopt. In this study we present the synthesis of the first nitroxides based on a spirocyclic pyrrolidine scaffold with an exocyclic methylene substituent. The conformations adopted by these nitroxides were evaluated by X-ray crystallography, both with single nitroxide crystals and by inclusion of nitroxides in a microporous crystalline sponge. The kinetic and thermodynamic stability of the new nitroxides towards reduction was investigated by electron paramagnetic resonance (EPR) spectroscopy and cyclic voltammetry (CV). In combination with EPR measurements of electron spin relaxation properties, these results suggest that this new family of nitroxides can provide access to multifunctionalized probes and polarising agents suitable for use in biological environments at elevated temperatures.

Liver cirrhosis: molecular mechanisms and therapeutic interventions.

Liver cirrhosis is the end-stage of chronic liver disease, characterized by inflammation, necrosis, advanced fibrosis, and regenerative nodule formation. Long-term inflammation can cause continuous damage to liver tissues and hepatocytes, along with increased vascular tone and portal hypertension. Among them, fibrosis is the necessary stage and essential feature of liver cirrhosis, and effective antifibrosis strategies are commonly considered the key to treating liver cirrhosis. Although different therapeutic strategies aimed at reversing or preventing fibrosis have been developed, the effects have not be more satisfactory. In this review, we discussed abnormal changes in the liver microenvironment that contribute to the progression of liver cirrhosis and highlighted the importance of recent therapeutic strategies, including lifestyle improvement, small molecular agents, traditional Chinese medicine, stem cells, extracellular vesicles, and gut remediation, that regulate liver fibrosis and liver cirrhosis. Meanwhile, therapeutic strategies for nanoparticles are discussed, as are their possible underlying broad application and prospects for ameliorating liver cirrhosis. Finally, we also reviewed the major challenges and opportunities of nanomedicine‒biological environment interactions. We hope this review will provide insights into the pathogenesis and molecular mechanisms of liver cirrhosis, thus facilitating new methods, drug discovery, and better treatment of liver cirrhosis.

Chloro-aluminum phthalocyanine encapsulation into liquid crystalline nanodispersions enhance skin penetration and phototoxicity in skin cancer cells

Non-melanoma skin cancer is one of the most common tumors in the world. Photodynamic therapy (PDT) is currently a non-invasive therapeutic option for the treatment of skin cancer and actinic keratosis. Chloro-aluminum phthalocyanine (AlClPc) is a second-generation photosensitizer that has been studied for application in PDT. However, it has the disadvantage of self-aggregating in a biological environment, which impairs its therapeutic action, making it a candidate for nanocarrier delivery. Among the nanocarriers, liquid crystalline nanodispersions (LCN) are biocompatible and present unique organizational characteristics that make them suitable for skin delivery of drugs. Herein, a new LCN based on oleic acid (OA), Phosal 75SA® containing or not D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) was developed and characterized aiming its application for skin cancer. The selected LCN with AlClPc showed nanometric size (152.3 ± 1.93 nm), adequate PDI (0.231 ± 0.009) and encapsulation efficiency (70.26 ± 3.87 %) and stability for 30 days. Also, LCN were characterized by polarized light microscopy and small angle X-ray diffraction (SAXS) resulting in hexagonal liquid crystalline nanodispersions. In the in vitro skin penetration test, LCN-AlClPc showed better penetration into the deeper skin layers than the control. LCN-AlClPc showed greater phototoxicity in the A431 tumor cell line than the control in the same cell line and also greater phototoxicity in A431 when compared to L929 fibroblast cells. Thus, LCN developed could improve the phototoxicity and skin penetration in vitro and are potential drug delivery systems for the treatment of non-melanoma skin cancer.

Nanomotor-Driven Targeting Chimeras as Accelerators for the Degradation of Extracellular Proteins.

Targeted protein degradation (TPD) is emerging as a therapeutic paradigm and a serviceable research tool in chemical biology and disease treatment. However, without driving sources, most targeting chimeras (TACs) lack the capability of self-diffusion and active searching in biological environments, which significantly impedes degradation efficiency. Herein, nanomotor-driven targeting chimeras (MotorTACs) are ingeniously designed to achieve effective internalization and degradation of extracellular platelet-derived growth factor (PDGF), a driver to cancer invasion and metastasis. Catalyzed by endogenous H2O2, MotorTACs diffused rapidly and searched actively in living cells, as visualized at the single-particle level under the dark-field mode. Hydrolysis efficiency is significantly enhanced as target protein degradation is complete in only 4h. Furthermore, MotorTACs-mediated degradation of PDGF is found to be via the lysosome and ubiquitin-proteasome dual-degradation pathways. Taking advantage of the properties, it is anticipated that MotorTACs provide a unique strategy against extracellular undruggable proteins, thus advancing the development of therapeutic interventions in chemical biology and disease treatment.

Sensitive electrochemical detection of methimazole based on a unique copper and exfoliated graphene oxide nanocomposite

Herein, we report the creation of a novel sensitive electrochemical sensing platform based on a copper and exfoliated graphene oxide (Cu-eGO) nanocomposite using a facile synthesis technique, which simultaneously removes the sodium ions that result from the exfoliation process to generate eGO from graphite. This novel Cu-eGO nanocomposite was characterized via SEM, EDX, Raman and XPS. The Cu-eGO/GCE exhibited much greater activity for the electrochemical oxidation of methimazole than the eGO/GCE or bare GCE. The electrochemical properties and kinetics involved in the oxidation of methimazole at the Cu-eGO were examined using voltammetry and electrochemical impedance spectroscopy (EIS). This Cu-eGO based sensing platform demonstrated high sensitivity at 1.32 μAμM−1cm−2, a low limit of detection at 0.06 μM, robust stability, and strong anti-interference against potential interferents that may exist in biological systems for the detection of methimazole. The developed electrochemical sensor was successfully employed in blood serum samples that mimicked real biological environments, showing its high applicability.

Enhanced eDNA monitoring for detection of viable harmful algal bloom species using propidium monoazide

This study investigated the use of propidium monoazide (PMA) to improve the accuracy of environmental DNA (eDNA) monitoring by selectively detecting intracellular DNA (iDNA) from living cells, while excluding extracellular DNA (exDNA) from dead organisms. eDNA samples were collected from various depths off the coast of Tongyeong, South Korea, and analyzed alongside environmental factors, such as temperature, dissolved oxygen, turbidity, and nutrient levels. The results showed that PMA-treated iDNA provided a more accurate estimate of viable harmful algal bloom species (HABs) than total eDNA and DNase-treated iDNA. Strong correlations were found between iDNA (PMA) and environmental factors, particularly nutrient levels and turbidity, suggesting its effectiveness in biological environments. The iDNA (PMA) concentrations were higher in the surface and bottom layers, indicating that these layers were more indicative of living organisms in marine environments. The application of PMA in eDNA monitoring reduces false positives and enhances the detection accuracy of viable HAB species, representing a promising tool for real-time monitoring and management of marine ecosystems.

Transitioning the production of lipidic mesophase-based delivery systems from lab-scale to robust industrial manufacturing following a risk-based quality by design approach augmented by artificial intelligence

Lipidic mesophase drug carriers have demonstrated the capacity to host and effectively deliver a wide range of active pharmaceutical ingredients, yet they have not been as extensively commercialized as other lipid-based products, such as liposomal delivery systems. Indeed, scientists are primarily focused on investigating the physics of these systems, especially in biological environments. Meanwhile, the production methods remain less advanced, and researchers are still uncertain about how the manufacturing process might affect the quality of formulations. Bringing these products to the market will require an industrial translation process. In this scenario, we have developed a robust strategy to produce lipidic mesophase-based drug delivery systems using a dual-syringe setup. We identified four critical process parameters in the newly developed method (dual-syringe method), in comparison to eight in the standard production method (gold standard), and we defined their optimal limits following a Quality by Design approach. The robustness and versatility of the proposed method were assessed experimentally by incorporating drugs with diverse physicochemical properties and augmented by machine learning which, by predicting the drug release from lipidic mesophases, reduces the formulation development time and costs.