Caffeine Release Research Articles

Nanotechnology-Driven Delivery of Caffeine Using Ultradeformable Liposomes-Coated Hollow Mesoporous Silica Nanoparticles for Enhanced Follicular Delivery and Treatment of Androgenetic Alopecia.

Androgenetic alopecia (AGA) is caused by the impact of dihydrotestosterone (DHT) on hair follicles, leading to progressive hair loss in men and women. In this study, we developed caffeine-loaded hollow mesoporous silica nanoparticles coated with ultradeformable liposomes (ULp-Caf@HMSNs) to enhance caffeine delivery to hair follicles. Caffeine, known to inhibit DHT formation, faces challenges in skin penetration due to its hydrophilic nature. We investigated caffeine encapsulated in liposomes, hollow mesoporous silica nanoparticles (HMSNs), and ultradeformable liposome-coated HMSNs to optimize drug delivery and release. For ultradeformable liposomes (ULs), the amount of polysorbate 20 and polysorbate 80 was varied. TEM images confirmed the mesoporous shell and hollow core structure of HMSNs, with a shell thickness of 25-35 nm and a hollow space of 80-100 nm. SEM and TEM analysis showed particle sizes ranging from 140-160 nm. Thermal stability tests showed that HMSNs coated with ULs exhibited a Td10 value of 325 °C and 70% residue ash, indicating good thermal stability. Caffeine release experiments indicated that the highest release occurred in caffeine-loaded HMSNs without a liposome coating. In contrast, systems incorporating ULp-Caf@HMSNs exhibited slower release rates, attributable to the dual encapsulation mechanism. Confocal laser scanning microscopy revealed that ULs-coated particles penetrated deeper into the skin than non-liposome particles. MTT assays confirmed the non-cytotoxicity of all HMSN concentrations to human follicle dermal papilla cells (HFDPCs). ULp-Caf@HMSNs promoted better cell viability than pure caffeine or caffeine-loaded HMSNs, highlighting enhanced biocompatibility without increased toxicity. Additionally, ULp-Caf@HMSNs effectively reduced ROS levels in DHT-damaged HFDPCs, suggesting they are promising alternatives to minoxidil for promoting hair follicle growth and reducing hair loss without increasing oxidative stress. This system shows promise for treating AGA.

New Insight for Enhanced Topical Targeting of Caffeine for Effective Cellulite Treatment: In Vitro Characterization, Permeation Studies, and Histological Evaluation in Rats

Cellulite (CLT) is one of the commonly known lipodystrophy syndromes affecting post-adolescent women worldwide. It is topographically characterized by an orange-peel, dimpled skin appearance hence, it is an unacceptable cosmetic problem. CLT can be modulated by surgical procedures such as; liposuction and mesotherapy. But, these options are invasive, expensive and risky. For these reasons, topical CLT treatments are more preferred. Caffeine (CA), is a natural alkaloid that is well-known for its prominent anti-cellulite effects. However, its hydrophilicity hinders its cutaneous permeation. Therefore, in the present study CA was loaded into solid lipid nanoparticles (SLNs) by high shear homogenization/ultrasonication. CA-SLNs were prepared using Compritol® 888 ATO and stearic acid as solid lipids, and span 60 and brij™35, as lipid dispersion stabilizing agents. Formulation variables were adjusted to obtain entrapment efficiency (EE > 75%), particle size (PS < 350 nm), zeta potential (ZP < −25 mV) and polydispersity index (PDI < 0.5). CA-SLN-4 was selected and showed maximized EE (92.03 ± 0.16%), minimized PS (232.7 ± 1.90 nm), and optimum ZP (−25.15 ± 0.65 mV) and PDI values (0.24 ± 0.02). CA-SLN-4 showed superior CA release (99.44 ± 0.36%) compared to the rest CA-SLNs at 1 h. TEM analysis showed spherical, nanosized CA-SLN-4 vesicles. Con-LSM analysis showed successful CA-SLN-4 permeation transepidermally and via shunt diffusion. CA-SLN-4 incorporated into Noveon AA−1® hydrogel (CA-SLN-Ngel) showed accepted physical/rheological properties, and in vitro release profile. Histological studies showed that CA-SLN-Ngel significantly reduced mean subcutaneous fat tissue (SFT) thickness with 4.66 fold (p = 0.035) and 4.16 fold (p = 0.0001) compared to CA-gel, at 7th and 21st days, respectively. Also, significant mean SFT thickness reduction was observed compared to untreated group with 4.83 fold (p = 0.0005) and 3.83 fold (p = 0.0043), at 7th and 21st days, respectively. This study opened new avenue for CA skin delivery via advocating the importance of skin appendages. Hence, CA-SLN-Ngel could be a promising nanocosmeceutical gel for effective CLT treatment.Graphical

Oxidised porous starch carrier for caffeine delivery: preparation, characterisation, and in vitro release

SummaryThis work established an oxidised porous starch carrier system for the administration of caffeine by selectively oxidising the main hydroxyl groups at the C6 positions of porous starch to carboxyl groups using 2,2,6,6‐tetramethylpiperidoxyl (TEMPO) oxidation. The loading capacity and encapsulation efficiency of oxidised porous starch on caffeine rose as the oxidation degree (0%–90%) increased, increasing by 4.66 and 4.95 times, respectively, at 90% oxidation. The crystallinity of porous starch diminished after TEMPO oxidation, while the crystalline caffeine transferred into an amorphous state when loaded onto oxidised porous starch. Following oxidation, the absolute value of porous starch surface potential rose, enabling the granules avoided aggregation. Caffeine formed tighter bonds with oxidised porous starch in acidic conditions due to the dissociation of carboxyl groups, which lead to a peak loading capacity (8.02%) of oxidised porous starch with 90% oxidation at pH 4. Electrostatic interactions and hydrogen bonds were the driving forces. Long‐term gastrointestinal release of caffeine was achieved utilising oxidised porous starch as carriers.

Mechanistic Investigation of Enzyme Triggered Release from a Xyloglucan Matrix Tablet for Controlled Colonic Drug Delivery

The objective of this study was to investigate the mechanisms underlying drug release from a controlled colonic release (CCR) tablet formulation based on a xyloglucan polysaccharide matrix and identify the factors that control the rate of release for the purpose of fundamentally substantiating the concept and demonstrating its robustness for colonic drug delivery. Previous work demonstrated in vitro limited release of 5-aminosalicylic acid (5-ASA) and caffeine from these tablets in small intestinal environment and significant acceleration of release by xyloglucanase, an enzyme of the colonic microbiome. Targeted colonic drug delivery was verified in an animal study in vivo. In the present work, interaction of the xyloglucan matrix tablets with aqueous dissolution media containing xyloglucanase was found to lead to the spontaneous formation of a hydrated highly viscous gummy layer at the surface of the matrix which had a reduced drug content compared to the underlying regions and persisted with a nearly constant thickness that was inversely correlated to the enzyme concentration throughout the duration of the release process. Enzymatic hydrolysis of xyloglucan was determined to take place at the surface of the matrix leading to matrix erosion and a relation for the rate of enzymatic reaction as a function of bulk enzyme concentration and the concentration of dissolved xyloglucan in the gummy layer was derived. A mathematical model was developed encompassing aqueous medium ingress, matrix metamorphosis due to xyloglucan dissolution and matrix swelling, enzymatic hydrolysis of the polysaccharide and concomitant drug release due to matrix erosion and simultaneous drug diffusion. The model was fitted to data of reducing sugar equivalents in the medium reflecting matrix erosion and released drug amount. Enzymatic reaction parameters and reasonable values of medium ingress velocity, xyloglucan dissolution rate constant and drug diffusion coefficient were deduced that provided an adequate approximation of the data. Erosion was shown to be the overwhelmingly dominant drug release mechanism while the role of diffusion marginally increased at low enzyme concentration and high drug solubility. Changing enzyme concentration had a rather weak effect on matrix erosion and drug release rate as demonstrated by model simulations supported by experimental data, while xyloglucan dissolution was slow and had a stronger effect on the rate of the process. Therefore, reproducible colonic drug delivery not critically influenced by inter- and intra-individual variation of microbial enzyme activity may be projected.

Evaluation of the responsiveness pattern to caffeine through a smart data-driven ECG non-linear multi-band analysis

This study aimed to explore more efficient ways of administering caffeine to the body by investigating the impact of caffeine on the modulation of the nervous system's activity through the analysis of electrocardiographic signals (ECG). An ECG non-linear multi-band analysis using Discrete Wavelet Transform (DWT) was employed to extract various features from healthy individuals exposed to different caffeine consumption methods: expresso coffee (EC), decaffeinated coffee (ED), Caffeine Oral Films (OF_caffeine), and placebo OF (OF_placebo). Non-linear feature distributions representing every ECG minute time series have been selected by PCA with different variance percentages to serve as inputs for 23 machine learning models in a leave-one-out cross-validation process for analyzing the behavior differences between ED/EC and OF_placebo/OF_caffeine groups, respectively, over time. The study generated 50-point accuracy curves per model, representing the discrimination power between groups throughout the 50 min. The best model accuracies for ED/EC varied between 30 and 70 %, (using the decision tree classifier) and OF_placebo/OF_caffeine ranged from 62 to 84 % (using Fine Gaussian). Notably, caffeine delivery through OFs demonstrated effective capacity compared to its placebo counterpart, as evidenced by significant differences in accuracy curves between OF_placebo/OF_caffeine. Caffeine delivery via OFs also exhibited rapid dissolution efficiency and controlled release rate over time, distinguishing it from EC. The study supports the potential of caffeine delivery through Caffeine OFs as a superior technology compared to traditional methods by means of ECG analysis. It highlights the efficiency of OFs in controlling the release of caffeine and underscores their promise for future caffeine delivery systems.

Pre-Treatment of Spent Coffee Grounds Using Hydrodynamic Cavitation

Spent coffee grounds (SCGs) constitute the main solid residue of the coffee brewing process. SCGs are generated in significant amounts daily, worldwide. The effective management of this waste through biological processes is still an unresolved problem. In this study, the application of hydrodynamic cavitation (HC) as a pre-treatment method for improving the biodegradability of SCGs suspended in municipal wastewater was proposed. An orifice plate with a conical concentric hole having inlet/outlet diameter of 3/10 mm was applied as the cavitation inducer. Three inlet pressures were chosen: 3, 5 and 7 bar. The effects in time intervals of 0, 5, 10, 20, 30 and 45 min were evaluated. The application of HC led to enhanced biodegradability for each case. The results of multi-criteria decision indicated that the most efficient combination in terms of biodegradability and energy usage was obtained at the pressure of 5 bar and duration of 20 or 30 min, depending on the adopted weights. The improvements of DOC/TOC (dissolved organic carbon/total organic carbon) ratio were 57% and 71%, as compared to the untreated samples. The release of caffeine was found at pressures of 5 and 7 bar. However, at 5 bar, this effect was noticed for the longest times, 30 and 45 min, respectively.

Photopolymer-Based Composite with Substance Release Capability Manufactured Additively with DLP Method.

In this study, caffeine-loaded photoresin composites with homogeneous structures, suitable for additive manufacturing of transdermal microneedle systems, were obtained. The properties of the composites with varying caffeine concentrations (0.1-0.4% w/w) were investigated for carbon-carbon double bond conversion using Fourier Transform Infrared Spectroscopy, surface wettability and mechanical properties using a static tensile test and nanoindentation, and caffeine release in ethanol using UV-Vis. The caffeine concentration did not affect the final degree of double bond conversion, which was confirmed in tensile tests, where the strength and Young's modulus of caffeine-loaded samples had comparable values to control ones. Samples with 0.1 and 0.2% caffeine content showed an increase in nanohardness and reduced elastic modulus of 50 MPa and 1.5 MPa, respectively. The good wettability of the samples with water and the increase in surface energy is a favorable aspect for the dedicated application of the obtained composite materials. The amount of caffeine released into the ethanol solution at 1, 3 and 7 days reached a maximum value of 81%, was higher for the lower concentration of caffeine in the sample and increased over time. The conducted research may enhance the potential application of composite materials obtained through the digital light processing method in additive manufacturing.

PBAT/PLA Films and Supercritical Impregnation of Caffeine for Potential Application in Anticellulite Tools

AbstractTopical administration is the preferred route for the controlled release of active compounds since it reduces side effects typical of other administration methods. The use of polymer blends is a way to modulate drug release from a topical device. The blends ensure modulation of a wide range of properties, such as mechanical properties, water sorption, and degradation. This paper proposes blends of poly(lactide acid) (PLA), and Poly(butylene adipate‐co‐terephthalate) (PBAT), for the topical release of caffeine, a molecule with anti‐inflammatory, antioxidant, and anticellulite activities. PBAT/PLA blends are optimized for compatibility between the two polymers, mechanical properties, and drug release rate. Blends with a higher amount of PBAT show the best performance regarding polymer compatibility. The blends undergo supercritical CO2‐assisted caffeine impregnation. This process assures homogeneous dispersion of caffeine into the polymer matrix. The ratios 45/55 and 55/45 PBAT/PLA show the best performance in terms of caffeine release (complete caffeine release within 25 h). Caffeine is released into three steps: a burst effect due to the caffeine dispersed over the film surface, a slower release due to the caffeine dispersed in the polymer matrix, and a fast release due to the increase of polymer degradation rate induced by caffeine presence.

Synthesis and Evaluation of Alginate-Based Nanogels as Sustained Drug Carriers for Caffeine.

The objective of this study is to design a polymeric network of nanogels for sustained release of caffeine. Therefore, alginate-based nanogels were fabricated by a free-radical polymerization technique for the sustained delivery of caffeine. Polymer alginate was crosslinked with monomer 2-acrylamido-2-methylpropanesulfonic acid by crosslinker N',N'-methylene bisacrylamide. The prepared nanogels were subjected to sol-gel fraction, polymer volume fraction, swelling, drug loading, and drug release studies. A high gel fraction was seen with the increasing feed ratio of polymer, monomer, and crosslinker. Greater swelling and drug release were observed at pH 4.6 and 7.4 as compared to pH 1.2 due to the deprotonation and protonation of functional groups of alginate and 2-acrylamido-2-methylpropanesulfonic acid. An increase was observed in swelling, loading, and release of the drug with the incorporation of a high feed ratio of polymer and monomer, while a reduction was seen with the increase in crosslinker feed ratio. Similarly, an HET-CAM test was used to evaluate the safety of the prepared nanogels, which showed that the prepared nanogels have no toxic effect on the chorioallantoic membrane of fertilized chicken eggs. Similarly, different characterizations techniques such as FTIR, DSC, SEM, and particle size analysis were carried out to determine the development, thermal stability, surface morphology, and particle size of the synthesized nanogels, respectively. Thus, we can conclude that the prepared nanogels can be used as a suitable agent for the sustained release of caffeine.

Preliminary Study on the Development of Caffeine Oral Solid Form 3D Printed by Semi-Solid Extrusion for Application in Neonates.

Apnea of prematurity can be treated with a body-weight-adjusted dosage of caffeine. Semi-solid extrusion (SSE) 3D printing represents an interesting approach to finely tailor personalized doses of active ingredients. To improve compliance and ensure the right dose in infants, drug delivery systems such as oral solid forms (orodispersible film, dispersive form, and mucoadhesive form) can be considered. The aim of this work was to obtain a flexible-dose system of caffeine by SSE 3D printing by testing different excipients and printing parameters. Gelling agents (sodium alginate (SA) and hydroxypropylmethyl cellulose (HPMC)) were used to obtain a drug-loaded hydrogel matrix. Disintegrants (sodium croscarmellose (SC) and crospovidone (CP)) were tested for get rapid release of caffeine. The 3D models were patterned by computer-aided design with variable thickness, diameter, infill densities, and infill patterns. The oral forms produced from the formulation containing 35% caffeine, 8.2% SA, 4.8% HPMC, and 52% SC (w/w) were found to have good printability, achieving doses approaching to those used in neonatology (between 3 and 10mg of caffeine for infants weighing approximately between 1 and 4kg). However, disintegrants, especially SC, acted more as binder/filler, showing interesting properties to maintain the shape after extrusion and enhance printability without a significant effect on caffeine release.

Caffeine Release from Magneto-Responsive Hydrogels Controlled by External Magnetic Field and Calcium Ions and Its Effect on the Viability of Neuronal Cells.

Caffeine (CAF) is a psychostimulant present in many beverages and with rapid bioabsorption. For this reason, matrices that effectuate the sustained release of a low amount of CAF would help reduce the intake frequency and side effects caused by high doses of this stimulant. Thus, in this study, CAF was loaded into magnetic gelatin/alginate (Gel/Alg/MNP) hydrogels at 18.5 mg/ghydrogel. The in vitro release of CAF was evaluated in the absence and presence of an external magnetic field (EMF) and Ca2+. In all cases, the presence of Ca2+ (0.002 M) retarded the release of CAF due to favorable interactions between them. Remarkably, the release of CAF from Gel/Alg/MNP in PBS/CaCl2 (0.002 M) at 37 °C under an EMF was more sustained due to synergic effects. In PBS/CaCl2 (0.002 M) and at 37 °C, the amounts of CAF released after 45 min from Gel/Alg and Gel/Alg/MNP/EMF were 8.3 ± 0.2 mg/ghydrogel and 6.1 ± 0.8 mg/ghydrogel, respectively. The concentration of CAF released from Gel/Alg and Gel/Alg/MNP hydrogels amounted to ~0.35 mM, thereby promoting an increase in cell viability for 48 h. Gel/Alg and Gel/Alg/MNP hydrogels can be applied as reservoirs to release CAF at suitable concentrations, thus forestalling possible side effects and improving the viability of SH-SY5Y cells.

Caffeine–Acrylic Resin DLP-Manufactured Composite as a Modern Biomaterial

Materials based on photocurable resins and pharmaceutically active agents (APIs) are gaining interest as a composite drug delivery system. In this study, a composite of caffeine with acrylic resin was obtained using an additive manufacturing method of digital light processing (DLP) as a potential material for transdermal drug delivery. The mechanical properties of the composites and the ability to release caffeine from the resin volume in an aqueous environment were investigated. The amount of caffeine in the resulting samples before and after release was evaluated using a gravimetric method. The global thresholding method was also evaluated for its applicability in examining caffeine release from the composite. It was shown that as the caffeine content increased, the strength properties worsened and the ability to release the drug from the composite increased, which was caused by negligible interfacial interactions between the hydrophilic filler and the hydrophobic matrix. The global thresholding method resulted in similar caffeine release rate values compared to the gravimetric method but only for samples in which the caffeine was mainly located near the sample surface. The distribution of caffeine throughout the sample volume made it impossible to assess the caffeine content of the sample using global thresholding.

Encapsulation of caffeine in sandwich structured Alyssum homolocarpum seed gum/PVA/gelatin nanofibers using electrospinning technique

In this study, multilayer sandwich nanofibers from Alyssum homolocarpum seed gum (AHSG), polyvinyl alcohol (PVA) and gelatin were created by electrospinning technique and used to encapsulate caffeine. The middle layer was prepared by electrospinning of AHSG and PVA with different mixing ratios. The average diameter of electrospun nanofibers decreased with increasing AHSG to PVA ratios. Due to their ideal morphology (smooth, uniform, and bead-free) and thinner fiber diameter, nanofibers with the volume ratio of 30:70 AHSG to PVA were chosen as the best sample for caffeine encapsulation. The second step involved spinning gelatin onto the AHSG/PVA nanofibers containing caffeine, as the outer layers. These nanofibers effectively trapped caffeine and had high thermal stability and amorphous structures. The multilayer nanofiber containing 1% caffeine had the highest encapsulation efficiency (88.2%). More than 50% of the caffeine in single-layer nanofiber was released into the saliva simulator environment in less than 60 s, but after that point the caffeine release slowed down gradually. Sandwich structured nanofibers were more resistant to caffeine release and had slower release rate. The Korsmeyer-Peppas model was chosen as the model that best describes the mechanism of caffeine release from single-layer and multi-layer nanofiber, and the release followed non-Fickian diffusion.

3D printing of LEGO® like designs with tailored release profiles for treatment of sleep disorder

3D printed LEGO®-like designs are an attractive approach for the development of compartmental delivery systems due to their potential for dose personalisation through the customisation of drug release profiles. Additive manufacturing technologies such as Fused Deposition Modelling (FDM) are ideal for the printing of structures with complex geometries and various sizes. This study is a paradigm for the fabrication of 3D printed LEGO® -like tablets by altering the design of the modular units and the filament composition for the delivery of different drug substances. By using a combination of placebo and drug loaded compartments comprising of immediate release (hydroxypropyl cellulose) and pH dependant polymers (hypromellose acetate succinate) we were able to customise the release kinetics of melatonin and caffeine that can potentially be used for the treatment of sleep disorders. The LEGO® -like compartments were designed to achieve immediate release of melatonin followed by variable lag times and controlled release of caffeine.

Modified Caffeine Release System and Its Immunomodulatory Effects on Breast Tumor Cells and Blood Phagocytes

Caffeine is an alkaloid present in a wide variety of plants. Currently the most consumed psychostimulant worldwide, its consumption is associated with several health benefits, including modulation of the innate and adaptive immune response, reduction of oxidative cellular stress, and decreased incidence of some cancers, including breast cancer. Breast cancer is the most common cause of cancer among women and the second leading cause of cancer death in women worldwide. The interaction between biomaterials and drugs has enabled a great advance in science for developing controlled drug delivery systems and has been used to treat numerous pathologies. This work aimed to evaluate the immunomodulatory effects of caffeine associated or not with polyethylene glycol adsorbed in microemulsion (MLP) on MCF-7 cells, phagocytic cells (MN), and coculture. For biological assays, ATCC (American Type Culture Collection, USA) cell lines of breast adenocarcinoma (MCF-7) and phagocytes (MN) obtained from voluntary donors were used. The cells (MN and MCF-7) and coculture were treated with caffeine and MLP and incubated for rheological characterization analyses: flow curve and viscosity, oxidative stress: superoxide anion assay (), and activity of the enzyme superoxide dismutase (Cu-Zn-SOD). Caffeine and MLP increased viscosity and blood and MCF-7 cells and affected the immunomodulation of oxidative stress metabolism of MN and MCF-7 cells treated with caffeine and associated caffeine to the MLP. These data suggest that caffeine is associated or not with MLP-induced immunomodulatory effects on MN phagocytes and MCF-7 cells, demonstrating the antitumor activity via oxidative stress and can be a complementary alternative for treating breast cancer.

Comparative Bioavailability and Benefits on Mental Functions of Novel Extended-Release Caffeine Capsules against Immediate-Release Caffeine Capsules: An Open-Label, Randomized, Cross-over, Single-Dose Two-Way Crossover Study

Present study aimed compared pharmacokinetic profile of sustained-release CaffXtend® capsules (SR-Caffeine) with immediate-release caffeine capsules (IR-Caffeine), and the effect of SR-caffeine on memory, motivation, concentration, and attention. This open-label, randomized, single-dose, two-treatment, two-sequence, two-period, two-way crossover oral bioavailability study block randomized (1:1) healthy subjects (N = 15) to receive SR-Caffeine (200 mg) and IR-Caffeine (200 mg). Blood samples were collected at 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36 and 48 h in each period. Primary study outcome included comparing relative bioavailability of SR-Caffeine 200 mg and IR-Caffeine 200 mg under fasting conditions, and changes in caffeine research visual analogue scale (Caff-VAS) scores (‘relaxed’, ‘alert’, ‘jittery’, ‘tired’, ‘tense’, ‘headache’, ‘overall mood’ and ‘mentally fatigued’) were also evaluated. Fifteen subjects completed the study. Mean tmax was 4.08 ± 2.13h for SR-Caffeine compared to 0.83 ± 0.39h for IR-Caffeine, (p < 0.0001). Similarly, mean t½ was 7.07 ± 3.48h for SR-Caffeine compared to 5.78 ± 2.11h for IR-Caffeine (p = 0.04189). However, total exposure was similar for SR-Caffeine and IR-Caffeine (90% CI: 89.89–120.50% to 94.49–123.82% for geometric least square mean of ln-transformed AUC0-t and AUC0-∞). In the Caff-VAS evaluation, the SR-Caffeine group showed significantly better scores for ‘jitteriness’, ‘tiredness’, ‘alertness’ and ‘overall mood’ for 8–12 h than the IR-Caffeine group. No adverse events were reported. Results demonstrated sustained release of caffeine over 24 h from SR-Caffeine as compared to IR-Caffeine, which showed significant improvements in the scores for ‘relaxed’, ‘alertness’ and ‘overall mood’ and significantly lower scores for the parameters-‘jittery’ and ‘tired’ for extended period. Clinical trial registration: CTRI/2021/06/034185

Synthesis and Electrochemical Evaluation of MSNs-PbAE Nanocontainers for the Controlled Release of Caffeine as a Corrosion Inhibitor.

In this paper, a controlled-release system of caffeine as a corrosion inhibitor was obtained by encapsulating it in MCM-41 silica nanoparticles coated with a poly(β-amino ester) (PbAE), a pH-sensible polymer. Encapsulation was verified using Fourier transform infrared spectroscopy (FTIR) and thermogravimetry (TGA). The release of caffeine from the nanocontainers was analyzed in electrolytes with pH values of 4, 5, and 7 using UV-Vis, showing a 21% higher release in acidic electrolytes than in neutral electrolytes, corroborating its pH sensitivity. Electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization were used to determine the inhibition mode and efficiency of the encapsulated and free caffeine. The caffeine released from the nanocontainers showed the highest efficiency, which was 85.19%. These results indicate that these nanocontainers could have potential use in smart anticorrosion coating applications.

Synthesis and characterization of a hydrophobic association hydrogel for drug delivery

This work reports the synthesis, characterization, and evaluation of a hydrophobic association hydrogel containing vinyl alginate (SA), acrylamide, and the hydrophobic molecule N,N'-(disulfanediylbis(4,1-phenylene))diacrylamide (SPDAAm) for release of drug very slightly water-soluble in water. The SPDAAm molecule was synthetized with acrylic acid and 4-Aminophenyl disulfide and further characterized by H1 NMR spectroscopy. The hydrogel was prepared with a crosslinking chemistry using vinyl SA and acrylamide in an aqueous surfactant solution at a concentration less than the (critical micellar concentration) CMC. The introduction of SPDAAm in the hydrogel increases the swelling degree owing to hydrophobic association. Furthermore, SPDAAm gives a pH-dependent and retardant effect for caffeine (CFN) release. At a pH of 7.4, the CFN release mechanism is controlled by swelling, macromolecular relaxation of the polymer, and erosion of the hydrogel. The hydrogel with SPDAAm shows acceptable biocompatibility and has potential applications as a biomaterial in controlled release of poorly water-soluble molecules, like CFN.

BMSCs overexpressed ISL1 reduces the apoptosis of islet cells through ANLN carrying exosome, INHBA, and caffeine.

Early apoptosis of grafted islets is one of the main factors affecting the efficacy of islet transplantation. The combined transplantation of islet cells and bone marrow mesenchymal stem cells (BMSCs) can significantly improve the survival rate of grafted islets. Transcription factor insulin gene enhancer binding protein 1 (ISL1) is shown to promote the angiogenesis of grafted islets and the paracrine function of mesenchymal stem cells during the co-transplantation, yet the regulatory mechanism remains unclear. By using ISL1-overexpressing BMSCs and the subtherapeutic doses of islets for co-transplantation, we managed to reduce the apoptosis and improve the survival rate of the grafts. Our metabolomics and proteomics data suggested that ISL1 upregulates aniline (ANLN) and Inhibin beta A chain (INHBA), and stimulated the release of caffeine in the BMSCs. We then demonstrated that the upregulation of ANLN and INHBA was achieved by the binding of ISL1 to the promoter regions of the two genes. In addition, ISL1 could also promote BMSCs to release exosomes with high expression of ANLN, secrete INHBA and caffeine, and reduce streptozocin (STZ)-induced islets apoptosis. Thus, our study provides mechanical insight into the islet/BMSCs co-transplantation and paves the foundation for using conditioned medium to mimic the ISL1-overexpressing BMSCs co-transplantation.

Caffeine Encapsulation in Metal Organic Framework MIL-53(Al) at Pilot Plant Scale for Preparation of Polyamide Textile Fibers with Cosmetic Properties.

Currently in the marketplace, we can find clothing items able to release skin-friendly ingredients while wearing them. These innovative products with high-added value are based on microencapsulation technology. In this work, due to its lightness, flexibility, porosity, chemical affinity and adsorption capacity, metal–organic framework (MOF) MIL-53(Al) was the selected microcapsule to be synthesized at a large scale and subsequent caffeine encapsulation. The synthesis conditions (molar ratio of reactants, solvents used, reaction time, temperature, pressure reached in the reactor and activation treatment to enhance the encapsulation capacity) were optimized by screening various scaling-up reactor volumes (from lab-scale of 40 mL to pilot plant production of 3.75 L). Two types of Al salts (Al(NO3)3·9H2O from the original recipe and Al2(SO4)3 as commercial SUFAL 8.2) were employed. The liporeductor cosmetic caffeine was selected as the active molecule for encapsulation. Caffeine (38 wt %) was incorporated in CAF@MIL-53(Al) microcapsules, as analyzed by TGA and corroborated by GC/MS and UV–vis after additive extraction. CAF@MIL-53(Al) microcapsules showed a controlled release of caffeine during 6 days at 25 °C (up to 22% of the initial caffeine). These capsules were incorporated through an industrial spinning process (with temperatures up to 260 °C) to manufacture PA-6 fibers with cosmetic properties. Up to 0.7 wt % of capsules were successfully incorporated into the fibers hosting 1700 ppm of caffeine. Fabrics were submitted to scouring, staining, and washing processes, detecting the presence of caffeine in the cosmetic fiber.