Search Results (35)

Hypocrellin A (HA) represents a pharmaceutically important perylenequinone photosensitizer produced by Shiraia bambusicola. However, submerged fermentation remains constrained by filamentous morphological characteristics and inherent mass transfer limitations. Although microparticle-enhanced cultivation (MPEC) has demonstrated efficacy in filamentous fungal systems, the molecular mechanisms by which physical cues, such as microparticle-induced shear stress, reprogram fungal metabolism remain largely unexplored. This work systematically optimizes SiO₂-based MPEC parameters for S. bambusicola GDMCC 60438, including particle dimensions, temporal addition protocols, and solid loading. Mechanistic investigations integrated pellet morphology analysis, membrane lipid composition, intracellular redox status, energy/precursor markers, and RNA-seq transcriptomic profiling with qRT-PCR validation. Under optimized conditions (10% w/v SiO₂, 30 mesh, added at 6 h), HA yield reached 41.76 ± 5.02 mg/L, representing a 3.65-fold increase over controls. MPEC shifted morphology toward smaller, more porous pellets with denser internal structure, accompanied by increased membrane fluidity (unsaturated/saturated fatty acid ratio from 1.54 to 2.63), elevated ROS levels with antioxidant enzyme activation, and enhanced acetyl-CoA and ATP accumulation. Transcriptomic analysis identified 206 differentially expressed genes enriched in oxidative phosphorylation, carbon metabolism, and stress responses, with upregulation of PKS-related biosynthetic genes and major facilitator superfamily transporters. This work establishes an integrated mechanistic framework linking particle-induced morphological changes to metabolic reprogramming through oxidative stress and subsequent transcriptional activation of the HA biosynthetic pathway, providing rational design principles for MPEC strategies in filamentous fungi. Full article

Background/Objectives: Oral surgical procedures in patients at risk of/diagnosed with MRONJ require systemic antibiotic therapy, which can fail to achieve an adequate local drug concentration. This research aims to design mucoadhesive buccal patches (containing erythromycin or the erythromycin–resveratrol combination) tailored to the therapeutic needs of patients at risk of MRONJ undergoing oral surgery. Methods: Erythromycin (ERY) and resveratrol (RSV) were embedded into lipid-based microparticles prepared via hot melt dispersion. The microparticles, recovered in the form of dry powders, were characterized in terms of yield, softening/melting temperature, active(s) content, physical state (amorphous vs. crystalline), and individual and bulk properties. Then, they were loaded into a hydrophilic gel, which was dried, obtaining microparticle-loaded buccal patches. The optimized patches were characterized in terms of uniformity, folding endurance, swelling, mucoadhesion, and oromucosal permeation/retention. Results: The microparticles were efficiently produced via a green approach, resulting in reproducible pharmaceutical powders with high loading efficacy (≈90%), spherical morphology, particle sizes in the range of approximately 106–425 μm, and a softening temperature close to body temperature. The buccal patches were also obtained via a green approach, and were found to be thin, flexible, homogeneous, highly swellable, extremely mucoadhesive, and able to promote ERY and RSV accumulation in the buccal tissue (≈25% and 2% of ERY and RSV, respectively, after 2 h) while avoiding active(s) absorption. Conclusions: The proposed buccal patches are viable candidates for further clinical trials aimed at evaluating both the effectiveness of locoregional antibiotic treatment and the usefulness of the co-administration of RSV and ERY. Full article

Background: The release study is a standard tool for the development, evaluation, and control of dosage forms. In the case of traditional drug delivery systems, it is conducted in accordance with the established principles available in the European and American Pharmacopoeias or guidelines proposed by registration agencies. The problem is the study of modern carriers, not yet described in compendia, which require adjustments to traditionally used methods. Objectives: The present study focuses on developing an optimal method for testing the release of cyclosporine (Cs, 0.5–4%) incorporated in solid lipid microparticles (SLM) dispersions (10%) intended for administration in the form of eye drops. This is a multicompartment lipid carrier that provides prolonged release of the active substance. Methods: Three methods of testing the release were compared: the dialysis bag method, the horizontal cells technique, and a method without a membrane. Results: During the analyses, the proper membrane was selected and the effect of the lysozyme enzyme on the release profile was analyzed. The effect of the composition of the acceptor fluid on the obtained results was also assessed. In the model without a membrane, up to 60% of the Cs was released within 30 min due to the burst effect. In horizontal chambers, no formulation released more than 14% of the Cs over 96 h, while at the same time, 60–70% of the Cs was released from the dialysis bag. Conclusions: Based on the obtained results, the dialysis bag method was selected to study the release of Cs from SLM without the need to use multicomponent artificial tear fluid as an acceptor medium. Full article

Solid lipid microparticles (SLMs) are multi-compartment lipid drug carriers that can be used in various forms via many routes of administration, primarily to obtain prolonged release, protect the drug substance or mask its taste. It is practically impossible to theoretically predict the effectiveness of the incorporation and distribution of active pharmaceutical ingredients (APIs) in SLMs, and these are fundamental features that determine the key properties of the dosage form. The possibility of an effective assessment of these features by selecting or developing sensitive, universal methods, therefore, conditions further development and practical use of this carrier. Therefore, unlike the already available review papers on SLMs, the aim of this mini-review is to focus solely on the issues of API distribution in SLMs and their release. For this purpose, the most important observations and results of our own research were collected and summarized, and then an attempt was made to confront them with the available literature data. Among the methods describing the critical attributes of SLMs, instrumental methods (DSC, AFM, Raman spectroscopy and NMR), quantitative studies for assessing API distribution in SLMs (including entrapment efficiency and drug-loading parameters) as well as different release techniques (without a membrane, in a dialysis bag and in horizontal chambers, taking into account physiological factors) were characterized and compared. The aim of this review is to facilitate the understanding of the SLM properties and to assess their ability to achieve the intended effect in vivo, as well as to standardize studies of such carriers, facilitating a comparison of the results between centers. Full article

Background/Objectives: This study aimed to develop gastroretentive tablets based on mucoadhesive–floating systems with encapsulated gentian (Gentiana lutea, Gentianaceae) root extract to overcome the low bioavailability and short elimination half-life of gentiopicroside, a dominant bioactive compound with systemic effect. The formulation also aimed to promote the local action of the extract in the stomach. Methods: Tablets were obtained by direct compression of sodium bicarbonate (7.5%) and solid lipid microparticles (92.5%), which were obtained with lyophilizing double emulsions. A quality by design (QbD) was employed to evaluate the impact of formulation factors and processing parameters on emulsion viscosity, powder characteristics (moisture content, encapsulation efficiency, flowability), and tablet characteristics (floating lag time, gentiopicroside release, and assessment of dispersibility during in vitro dissolution). Results: The trehalose content and high-shear-homogenization (HSH) time of primary emulsion were critical factors. Trehalose content positively influenced emulsion viscosity, moisture content, floating lag time, encapsulation efficiency, and the release rate of gentiopicroside. HSH time positively affected powder stability and negatively gentiopicroside release. The selected powder had a high gentiopicroside encapsulation efficiency (95.13%), optimal stability, and good flowability. The developed tablets exhibited adequate floating lag time (275 s), mucoadhesive properties, and gentiopicroside biphasic release (29.04% in 45 min; 67.95% in 6 h). Furthermore, the optimal tablet formulation remained stable for 18 months and was primarily digested by duodenal enzymes. Conclusions: Dual-mechanism gastroretentive tablets with encapsulated gentian root extract were successfully developed. The in vitro digestion study demonstrated that the optimal formulation effectively resisted gastric enzymes, ensuring the release of its contents in the small intestine, even in the case of premature gastric evacuation. Full article

Ursolic acid (UA) and oleanolic acid (OA) are hydrophobic triterpenoid isomers with demonstrated anti-mycobacterial (Mtb) and immune-regulatory properties, although their poor solubility limits clinical use. We report the development of solid lipid microparticles (SLMs) as delivery vehicles for UA and OA and evaluate their anti-Mtb efficacy in vitro and in vivo, as well as their acute toxicity. SLMs measured 0.7–0.89 µM in size, with complete in vitro release of OA and UA at 40 and 32 h, respectively. The minimum inhibitory concentration (MIC) of SLMs loaded with OA and UA was 40 µg/mL SLMs + 20 µg/mL OA + 20 µg/mL UA for drug-sensitive Mtb and 80 µg/mL SLMs + 40 µg/mL OA + 40 µg/mL UA for multidrug-resistant (MDR) Mtb. These SLMs showed an efficient reduction in Mtb burden in infected alveolar macrophages. In a murine model of late-stage progressive MDR-TB, aerosolized delivery of SLMs containing OA and UA via a metered-dose inhaler significantly reduced pulmonary bacterial loads and extended survival. In vivo, acute toxicity studies revealed no mortality or signs of toxicity. These findings demonstrate that SLMs are an optimal delivery system for terpenoids, providing potent in vitro and in vivo anti-TB activity with an excellent safety profile. Full article

Fumaric acid, a naturally occurring preservative with antimicrobial properties, has been widely used in the baking industry. However, its direct addition interferes with yeast activity and negatively impacts the gluten structure. This study investigates the potential of spray-congealing as a method for encapsulating fumaric acid within solid lipid microparticles. The selection of lipid carriers and surfactants is critical, so hydrogenated palm stearin, hydrogenated rapeseed oil, and Compritol ATO 888 (glyceryl behenate) were chosen as lipid carriers, and propylene glycol monostearate and glyceryl monolaurate were utilised as surfactants with varying concentrations. Rheological properties, encapsulation efficiency, particle size, moisture content, and thermal behaviour were assessed, along with the release profiles under different temperature conditions simulating the baking process. The findings indicate that the addition of surfactants significantly impacts the viscosity and stability of the molten mixtures, which in turn affects the spray-congealing process and the release of fumaric acid. The temperature-dependent and time-dependent release profiles demonstrate the potential for customising release kinetics to suit specific applications, such as the baking industry. This study may contribute to the development of a controlled-release system that synchronises with the baking process, thereby optimising fumaric acid’s functionality while preserving the quality of baked goods. Full article

The present study aimed to investigate the properties of calcium-rich soy protein isolate (SPI) gels (14% SPI; 100 mM CaCl₂), the effects of incorporating different concentrations locust bean gum (LBG) (0.1–0.3%, w/v) to the systems and the stability of the obtained gels. Also, the incorporation of solid lipid microparticles (SLMs) was tested as an alternative strategy to improve the system’s stability and, therefore, potential to be applied as a product prototype. The gels were evaluated regarding their visual aspect, rheological properties, water-holding capacities (WHCs) and microstructural organizations. The CaCl₂-induced gels were self-supported but presented low WHC (40.0% ± 2.2) which was improved by LBG incorporation. The obtained mixed system, however, presented low stability, with high syneresis after 10 days of storage, due to microstructural compaction. The gels’ stability was improved by SLM incorporation, which decreased the gelled matrices’ compaction and syneresis for more than 20 days. Even though the rheological properties of the emulsion-filled gels (EFGs) were very altered due to the ageing process (which may affect the sensory perception of a future food originated from this EFG), the incorporation of SLMs increased the systems potential to be applied as a calcium-rich product prototype. Full article

Ferulic acid (Fer) and geraniol (Ger) are natural compounds whose antioxidant and anti-inflammatory activity confer beneficial properties, such as antibacterial, anticancer, and neuroprotective effects. However, the short half-lives of these compounds impair their therapeutic activities after conventional administration. We propose, therefore, a new prodrug (Fer-Ger) obtained by a bio-catalyzed ester conjugation of Fer and Ger to enhance the loading of solid lipid microparticles (SLMs) designed as Fer-Ger delivery and targeting systems. SLMs were obtained by hot emulsion techniques without organic solvents. HPLC-UV analysis evidenced that Fer-Ger is hydrolyzed in human or rat whole blood and rat liver homogenates, with half-lives of 193.64 ± 20.93, 20.15 ± 0.75, and 3.94 ± 0.33 min, respectively, but not in rat brain homogenates. Studies on neuronal-differentiated mouse neuroblastoma N2a cells incubated with the reactive oxygen species (ROS) inductor H₂O₂ evidenced the Fer-Ger ability to prevent oxidative injury, despite the fact that it appears ROS-promoting. The amounts of Fer-Ger encapsulated in tristearin SLMs, obtained in the absence or presence of glucose, were 1.5 ± 0.1%, allowing the control of the prodrug release (glucose absence) or to sensibly enhance its water dissolution rate (glucose presence). These new “green” carriers can potentially prolong the beneficial effects of Fer and Ger or induce neuroprotection as nasal formulations. Full article

The aim of this study was to assess the impact of physiological factors, namely tear fluid and lysozyme enzyme, as well as surfactant polysorbate, on the release profile from solid lipid microparticles (SLM), in the form of dispersion intended for ocular application. Indomethacin (Ind) was used as a model drug substance and a release study was performed by applying the dialysis bag method. Conducting release studies taking into account physiological factors is expected to improve development and screening studies, as well as support the regulatory assessment of this multi-compartment lipid dosage form. The effect of the lysozyme was directly related to its effect on lipid microparticles, as it occurred only in their presence (no effect on the solubility of Ind). Polysorbate also turned out to be an important factor interacting with the SLM surface, which determined the release of Ind from SLM. However, in study models without tear fluid or lysozyme, the release of Ind did not exceed 60% within 96 h. Ultimately, only the simultaneous application of artificial tear fluid, lysozyme, and polysorbate allowed for the release of 100% of Ind through the SLM dispersion. The examination of the residues after the release studies indicated the possibility of releasing 100% of Ind from SLM without complete degradation of the microparticles’ matrix. The incubation of SLM with tear fluid confirmed a similar influence of physiological factors contained in tear fluid on the surface structure of SLM as that observed during the in vitro studies. Full article

In the presented study, an attempt was made to investigate the most important attributes of solid lipid microparticles (SLM) using thermal analysis (DSC/TG) in order to determine the importance of this technique in the research and development of lipid microparticles. Particularly interesting in our studies were drug–lipid interactions and modifications of the SLM matrix structure induced by the production method (the hot emulsification method) and further processing (e.g., spray drying), as well as changes occurring during the stability studies. Cyclosporine A, indomethacin and spironolactone were used as model active substances incorporated into SLM. The conducted research demonstrated the significant potential of DSC/TG, especially for the analysis of SLM in the form of fine powder. The method of sample preparation, consisting of evaporation of water at room temperature, turned out to be crucial for the DSC/TG analysis of SLM dispersion. In the case of the tested SLM, the basic and usually the only observed thermal transformation in the DSC spectrum was the endothermic peak associated with the lipid forming a microsphere matrix. This peak is the main source of information about the properties and stability of the tested SLM. The obtained results show that glyceryl behenate (Compritol) is a significantly better lipid for forming lipid microparticles than stearic acid. Although thermal transformations of the incorporated drug substances are not directly visible in the DSC spectra, their impact on the SLM properties can be assessed indirectly, based on changes in the lipid melting point and the shape of the DSC and TG peaks and curves. DSC/TG studies confirmed the lack of an effect of the spray drying process on the properties of drug-loaded SLM with Compritol. Studies have also shown up to a 2-year stability of SLM with CsA. Full article

The objective of this study was to develop effervescent cleansing tablets that can be dissolved and turned into liquid soap, which can be used for bathing or soaking the body. The asiatic-acid-loaded solid lipid microparticles (AASLMs) were prepared via the hot emulsification method followed by cold re-solidification and then freeze-dried to obtained dry powder. The physicochemical properties such as morphology and % entrapment efficiency (%EE) were evaluated. The results revealed that AASLMs have an irregular shape, and the %EE for the resulting AASLMs was 92.04 ± 3.43%. The tablets were manufactured via the direct compression technique. The compatibility test was conducted to ensure that the excipients are compatible with the active ingredient. The angle of repose, Carr’s index, and Hausner’s ratio were studied to evaluate the flowability of the powder blend before compression. The weight of each tablet was set to 1000 mg, and physicochemical characteristics, in vitro dissolution, ex vivo cleansing efficacy, and stability were evaluated. The results showed that the active ingredient was compatible with other excipients, as the results obtained from FTIR spectra indicated the absence of potential chemical interaction between the active ingredient and excipients used in this study. Additionally, all formulations had good flow properties. The effervescence times of selected formulations, F2 and F3, were <5 min, with favorable pH and hardness values. The friability values of all formulations exceeded 1% because the excipients used in effervescent tablets are very fragile. The release of asiatic acid (AA) from the tablets was dependent on the concentration of SLS. In an ex vivo test, it was discovered that the developed products F2 and F3 showed much more effective cleansing efficacy than water. Nevertheless, brown spots appeared in the tablets and the AA content was significantly decreased in both tested formulations after 3 months’ storage at 40 ± 2 °C/75% RH ± 5% RH. The stability study revealed that the developed products were not stable at high temperature and humidity. Therefore, it is recommended that the developed effervescent tablets are not stored at a high temperature. Full article

Microfluidic technology has emerged as a powerful tool for several applications, including chemistry, physics, biology, and engineering. Due to the laminar regime, droplet-based microfluidics enable the development of diverse delivery systems based on food-grade emulsions, such as multiple emulsions, microgels, microcapsules, solid lipid microparticles, and giant liposomes. Additionally, by precisely manipulating fluids on the low-energy-demand micrometer scale, it becomes possible to control the size, shape, and dispersity of generated droplets, which makes microfluidic emulsification an excellent approach for tailoring delivery system properties based on the nature of the entrapped compounds. Thus, this review points out the most current advances in droplet-based microfluidic processes, which successfully use food-grade emulsions to develop simple and complex delivery systems. In this context, we summarized the principles of droplet-based microfluidics, introducing the most common microdevice geometries, the materials used in the manufacture, and the forces involved in the different droplet-generation processes into the microchannels. Subsequently, the encapsulated compound type, classified as lipophilic or hydrophilic functional compounds, was used as a starting point to present current advances in delivery systems using food-grade emulsions and their assembly using microfluidic technologies. Finally, we discuss the limitations and perspectives of scale-up in droplet-based microfluidic approaches, including the challenges that have limited the transition of microfluidic processes from the lab-scale to the industrial-scale. Full article

The release profiles of active substances from microspheres are one of the most important features in solid lipid microparticles (SLM) characterization. Unfortunately, the results of the dissolution tests are largely dependent on the chosen method and test conditions, which in relation to novel dosage forms, such as dispersions of lipid microspheres, are not clearly defined in international compendiums and guidelines. This makes it impossible to compare the results of different studies. The aim of the research was to identify the factors most influencing the variability of the obtained results. An attempt was also made to select the most appropriate method for testing drug substance release from SLM. Various dissolution methods were employed (method I: without a membrane, method II: in a dialysis bag, and method III: in a Side-Bi-Side chamber), and the obtained release profiles of cyclosporine and indomethacin from SLM dispersions were compared. In addition to the effect of membranes, the types of acceptor fluids were also investigated. Significant differences were observed when testing the SLM formulations under various test conditions. The results were significantly influenced by the selected membrane, the acceptor fluid, or the difference in the concentrations of active substance between the donor and acceptor compartments. The burst effect observed in some experimental methods was not noticed in other conditions. At this stage, the method with a dialysis bag has been selected as the most suitable, while the methods without the membrane can only play a complementary role. Full article

Reformulating poorly water-soluble drugs as supersaturated lipid-based formulations achieves higher drug loading and potentially improves solubilisation and bioavailability. However, for the weak base blonanserin, silica solidified supersaturated lipid-based formulations have demonstrated reduced in vitro solubilisation compared to their liquid-state counterparts. Therefore, this study aimed to understand the influence of supersaturated drug load on blonanserin solubilisation from liquid and silica solidified supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) during in vitro lipolysis. Stable liquid super-SNEDDS with varying drug loads (90–300% of the equilibrium solubility) were solidified by imbibition into porous silica microparticles (1:1 lipid: silica ratio). In vitro lipolysis revealed greater blonanserin solubilisation from liquid super-SNEDDS compared to solid at equivalent drug saturation levels, owing to strong silica-BLON/lipid interactions, evidenced by a significant decrease in blonanserin solubilisation upon addition of silica to a digesting liquid super-SNEDDS. An increase in solid super-SNEDDS drug loading led to increased solubilisation, owing to the increased drug:silica and drug:lipid ratios. Solidifying SNEDDS with silica enables the fabrication of powdered formulations with higher blonanserin loading and greater stability than liquid super-SNEDDS, however at the expense of drug solubilisation. These competing parameters need careful consideration in designing optimal super-SNEDDS for pre-clinical and clinical application. Full article