PVP/aprepitant microcapsules produced by supercritical antisolvent process.

The supercritical antisolvent (SAS) process was a green alternative to improve the low bioavailability of insoluble drugs. However, it is difficult for SAS process to industrialize with limited production capacity. A coaxial annular nozzle was used to prepare the microcapsules of aprepitant (APR) and polyvinylpyrrolidone (PVP) by SAS with N, N-Dimethylformamide (DMF) as solvent. Meanwhile, the effects of polymer/drug ratio, operating pressure, operating temperature and overall concentration on particles morphology, mean particle diameter and size distribution were analyzed. Microcapsules with mean diameters ranging from 2.04 µm and 9.84 µm were successfully produced. The morphology, particle size, thermal behavior, crystallinity, drug content, drug dissolution and residual amount of DMF of samples were analyzed. The results revealed that the APR drug dissolution of the microcapsules by SAS process was faster than the unprocessed APR. Furthermore, the drug powder collected every hour is in the kilogram level, verifying the possibility to scale up the production of pharmaceuticals employing the SAS process from an industrial point of view.

Optimization of Hypericum Perforatum Microencapsulation Process by Spray Drying Method.

Hypericum perforatum (HP) contains valuable and beneficial bioactive compounds that have been used to treat or prevent several illnesses. Encapsulation technology offers protection of the active compounds and facilitates to expose of the biologically active compounds in a controlled mechanism. Microcapsulation of the hydroalcoholic gum arabic and maltodextrin have hot been used as wall materials in the encapsulation of HP extract. Therefore, the optimum microencapsulation parameters of Hypericum perforatum (HP) hydroalcoholic extract were determined using response surface methodology (RSM) for the evaluation of HP extract. Three levels of three independent variables were screened using the one-way ANOVA. Five responses were monitored, including total phenolic content (TPC), 2,2-Diphenyl-1-picrylhydrazyl (DPPH), carr index (CI), hausner ratio (HR), and solubility. Optimum drying conditions for Hypericum perforatum microcapsules (HPMs) were determined: 180 °C for inlet air temperature, 1.04/1 for ratio of maltodextrin to gum arabic (w/w), and 1.98/1 for coating to core material ratio (w/w). TPC, antioxidant activity, CI, HR, and solubility values were specified as 316.531 (mg/g GAE), 81.912%, 6.074, 1.066, and 35.017%, respectively, under the optimized conditions. The major compounds of Hypericum perforatum (hypericin and pseudohypericin) extract were determined as 4.19 µg/g microcapsule and 15.09 µg/g microcapsule, respectively. Scanning electron microscope (SEM) analysis revealed that the mean particle diameter of the HPMs was 20.36 µm. Based on these results, microencapsulation of HPMs by spray drying is a viable technique which protects the bioactive compounds of HP leaves, facilitating its application in the pharmaceutical, cosmetic, and food industries.

Microencapsulation of Essential Oils Using Faba Bean Protein and Chia Seed Polysaccharides via Complex Coacervation Method.

The aim of this study was to develop microcapsules containing juniper or black pepper essential oils, using a combination of faba bean protein and chia seed polysaccharides (in ratios of 1:1, 1:2, 2:1). By synergizing these two polymers, our goal was to enhance the efficiency of essential oil microencapsulation, opening up various applications in the food industry. Additionally, we aimed to investigate the influence of different polymer mixing ratios on the properties of the resulting microcapsules and the course of the complex coacervation process. To dissolve the essential oils and limit their evaporation, soybean and rapeseed oils were used. The powders resulting from the freeze-drying of coacervates underwent testing to assess microencapsulation efficiency (65.64-87.85%), density, flowability, water content, solubility, and hygroscopicity. Additionally, FT-IR and DSC analyses were conducted. FT-IR analysis confirmed the interactions between the components of the microcapsules, and these interactions were reflected in their high thermal resistance, especially at a protein-to-polysaccharide ratio of 2:1 (177.2 °C). The water content in the obtained powders was low (3.72-7.65%), but it contributed to their hygroscopicity (40.40-76.98%).

Adenosine Encapsulation and Characterization through Layer-by-Layer Assembly of Hydroxypropyl-ß-Cyclodextrin and Whey Protein Isolate as Wall Materials.

Adenosine, as a water-soluble active substance, has various pharmacological effects. This study proposes a layer-by-layer assembly method of composite wall materials, using hydroxypropyl-ß-cyclodextrin as the inner wall and whey protein isolate as the outer wall, to encapsulate adenosine within the core material, aiming to enhance adenosine microcapsules' stability through intermolecular interactions. By combining isothermal titration calorimetry with molecular modeling analysis, it was determined that the core material and the inner wall and the inner wall and the outer wall interact through intermolecular forces. Adenosine and hydroxypropyl-ß-cyclodextrin form an optimal 1:1 complex through hydrophobic interactions, while hydroxypropyl-ß-cyclodextrin and whey protein isolate interact through hydrogen bonds. The embedding rate of AD/Hp-ß-CD/WPI microcapsules was 36.80%, and the 24 h retention rate under the release behavior test was 76.09%. The method of preparing adenosine microcapsules using composite wall materials is environmentally friendly and shows broad application prospects in storage and delivery systems with sustained release properties.

Enzymatically produced acylglycerol and glycerin monostearate additives improved the characteristics of gelatin-stabilized omega-3 emulsions and microcapsules.

The impacts of enzymatically produced acylglycerol and glycerin monostearate on the characteristics of gelatin-stabilized omega-3 emulsions and microcapsules were investigated. Tuna oil was enzymatically produced and the resulting acylglycerol was mixed with tuna oil at 12.5% (w/w) to prepare a novel oil phase. This oil phase was stabilized by gelatin to prepare oil-in-water emulsions and subsequent microcapsules via complex coacervation. The tuna oil with glycerin monostearate (GMS) at 1 and 2% (w/w) were used as controls. Results showed that both acylglycerol and GMS significantly reduced the emulsion droplet size and zeta potential, while increasing the viscoelasticity and stability. The diacylglycerol/monoacylglycerol were involved in the oil/water interfacial layer formation by lowering interfacial tension and increasing droplet surface hydrophobicity. Overall, the changed emulsion properties promoted the complex coacervation and contributed to the formation of microcapsules with improved oxidative stability. Therefore, enzymatically produced acylglycerol can develop high-quality stable omega-3 microencapsulated novel food ingredients.

In Vitro Simulation of the Fasted Gastric Conditions and Their Variability to Elucidate Contrasting Properties of the Marketed Dabigatran Etexilate Pellet-Filled Capsules and Loose Pellets.

Variability of the gastrointestinal tract is rarely reflected in in vitro test protocols but often turns out to be crucial for the oral dosage form performance. In this study, we present a generation method of dissolution profiles accounting for the variability of fasted gastric conditions. The workflow featured 20 biopredictive tests within the physiological variability. The experimental array was constructed with the use of the design of experiments, based on three parameters: gastric pH and timings of the intragastric stress event and gastric emptying. Then, the resulting dissolution profiles served as a training data set for the dissolution process modeling with the machine learning algorithms. This allowed us to generate individual dissolution profiles under a customizable gastric pH and motility patterns. For the first time ever, we used the method to successfully elucidate dissolution properties of two dosage forms: pellet-filled capsules and bare pellets of the marketed dabigatran etexilate product Pradaxa. We showed that the dissolution of capsules was triggered by mechanical stresses and thus was characterized by higher variability and a longer dissolution onset than observed for pellets. Hence, we proved the applicability of the method for the in vitro and in silico characterization of immediate-release dosage forms and, potentially, for the improvement of in vitro-in vivo extrapolation.

Sunflower pollen-derived microcapsules adsorb light and bacteria for enhanced antimicrobial photothermal therapy.

Bacterial infection is one of the most serious clinical complications, with life-threatening outcomes. Nature-inspired biomaterials offer appealing microscale and nanoscale architectures that are often hard to fabricate by traditional technologies. Inspired by the light-harvesting nature, we engineered sulfuric acid-treated sunflower sporopollenin exine-derived microcapsules (HSECs) to capture light and bacteria for antimicrobial photothermal therapy. Sulfuric acid-treated HSECs show a greatly enhanced photothermal performance and a strong bacteria-capturing ability against Gram-positive bacteria. This is attributed to the hierarchical micro/nanostructure and surface chemistry alteration of HSECs. To test the potential for clinical application, an in situ bacteria-capturing, near-infrared (NIR) light-triggered hydrogel made of HSECs and curdlan is applied in photothermal therapy for infected skin wounds. HSECs and curdlan suspension that spread on bacteria-infected skin wounds of mice first capture the local bacteria and then form hydrogels on the wound upon NIR light stimulation. The combination shows a superior antibacterial efficiency of 98.4% compared to NIR therapy alone and achieved a wound healing ratio of 89.4%. The current study suggests that the bacteria-capturing ability and photothermal properties make HSECs an excellent platform for the phototherapy of bacteria-infected diseases. Future work that can fully take advantage of the hierarchical micro/nanostructure of HSECs for multiple biomedical applications is highly promising and desirable.

Effect of photoconversion conditions on the spectral and cytotoxic properties of photoconvertible fluorescent polymer markers.

Fluorescence labeling of cells is a versatile tool used to study cell behavior, which is of significant importance in biomedical sciences. Fluorescent photoconvertible markers based on polymer microcapsules have been recently considered as efficient and perspective ones for long-term tracking of individual cells. However, the dependence of photoconversion conditions on the polymeric capsule structure is still not sufficiently clear. Here, we have studied the structural and spectral properties of fluorescent photoconvertible polymeric microcapsules doped with Rhodamine B and irradiated using a pulsed laser in various regimes, and shown the dependence between the photoconversion degree and laser irradiation intensity. The effect of microcapsule composition on the photoconversion process was studied by monitoring structural changes in the initial and photoconverted microcapsules using X-ray diffraction analysis with synchrotron radiation source, and Fourier transform infrared, Raman and fluorescence spectroscopy. We demonstrated good biocompatibility of free-administered initial and photoconverted microcapsules through long-term monitoring of the RAW 264.7 monocyte/macrophage cells with unchanged viability. These data open new perspectives for using the developed markers as safe and precise cell labels with switchable fluorescent properties.

Integration of metal organic framework nanoparticles into sodium alginate biopolymer-based three-dimensional membrane capsules for the efficient removal of toxic metal cations from water and real sewage.

Sodium alginate (SA) biopolymer has been recognized as an efficient adsorbent material owing to their unique characteristics, including biodegradability, non-toxic nature, and presence of abundant hydrophilic functional groups. Accordingly, in the current research work, UiO-66-OH and UiO-66-(OH)2 metal organic framework (MOF) nanoparticles (NPs) have been integrated into SA biopolymer-based three-dimensional (3-D) membrane capsules (MCs) via a simple and facile approach to remove toxic metal cations (Cu2+ and Cd2+) from water and real sewage. The newly configured capsules were characterized by FTIR, SEM, XRD, EDX and XPS analyses techniques. Exceptional sorption properties of the as-developed capsules were ensured by evaluation of the pertinent operational parameters, i.e., contents of MOF-NPs (1-100 wt%), adsorbent dosage (0.001-0.05 g), content time (0-360 h), pH (1-8), initial concentration of metal cations (5-1000 mg/L) and reaction temperature (298.15-333.15 K) on the eradication of Cu2+ and Cd2+ metal cations. It was found that hydrophilic functional groups (-OH and -COOH) have performed an imperative role in the smooth loading of MOF-NPs into 3-D membrane capsules via intra/inter-molecular hydrogen bonding and van der waals potencies. The maximum monolayer uptake capacities (as calculated by the Langmuir isotherm model) of Cd2+ and Cu2+ by 3-D SGMMCs-OH were 940 and 1150 mg/g, respectively, and by 3-D SGMMCs-(OH)2 were 1375 and 1575 mg/g, respectively, under optimum conditions. The as-developed capsules have demonstrated superior selectivity against targeted metal cations under designated pH and maintained >80 % removal efficiency up to six consecutive treatment cycles. Removal mechanisms of metal cations by the 3-D SGMMCs-OH/(OH)2 was proposed, and electrostatic interaction, ion-exchange, inner-sphere coordination bonds/interactions, and aromatic ligands exchange were observed to be the key removal mechanisms. Notably, FTIR and XPS analysis indicated that hydroxyl groups of Zr-OH and BDC-OH/(OH)2 aromatic linkers played vital roles in Cu2+ and Cd2+ adsorption by participating in inner-sphere coordination interactions and aromatic ligands exchange mechanisms. The as-prepared capsules indicated >70 % removal efficiency of Cu2+ from real electroplating wastewater in the manifestation of other competitive metal ions and pollutants under selected experimental conditions. Thus, it was observed that newly configured 3-D SGMMCs-OH/(OH)2 have offered a valuable discernment into the development of MOFs-based water decontamination 3-D capsules for industrial applications.

Yeast cell wall capsules for delivery of oat biomarker avenanthramide-C.

Avenanthramide-C (AVN-C) is the biomarker for oat with a variety of physiological functions, whereas its application is constrained by low stability and bioavailability. Avenanthramide-C is the biomarker for oat with a variety of physiological functions, whereas its application is constrained by low stability and bioavailability. This study evaluated the potential of yeast cell (YC) and yeast cell wall (YCW) capsules as delivery systems for stabilizing AVN-C. It was observed that these yeast capsules possessed the ellipsoidal morphology and intact structure without visual pores. Additionally, the YCW capsules exhibited higher encapsulation and loading capacity due to the large internal space. The interaction of yeast capsules with AVN-C involved the hydrophobic interactions and hydrogen bonding. Moreover, the loading of AVN-C induced high hydrophobicity inside the yeast capsules, which helped to protect AVN-C against degradation and release AVN-C in a slow and sustained manner in the simulated gastrointestinal tract. The YCW capsules have potential as controlled delivery system for AVN-C, which could be further used as a nutraceutical and added to functional foods.

Facile fabrication of microfibrillated cellulose-based aerogels incorporated with nisin/ß-cyclodextrin microcapsule for channel catfish preservation.

In this study, a hydrophobic and antibacterial pad was prepared to preserve Channel Catfish (Ictalurus punctatus). The pad composite the microfibrillated cellulose and ß-cyclodextrin/nisin microcapsules. The hydrophobic pad ensures a dry surface in contact with the fish, reducing microbial contamination. The pad has a low density and high porosity, making it lightweight and suitable for packaging applications, while also providing a large surface area for antibacterial activity. Results demonstrated that this antibacterial pad exhibits an ultralow density of 9.0 mg/cm3 and an ultrahigh porosity of 99.10%. It can extend the shelf life of Channel Catfish fillets to 9 days at 4 °C, with a total volatile base nitrogen below 20 mg/100 g. The study proposes a novel solution for preserving aquatic products by combining antibacterial substances with the natural base material aerogel. This approach also extends the utilization of aerogel and nisin in food packaging.

Peptide-functionalized chitosan-based microcapsules for dual active targeted treatment of lung infections.

Lung infections, such as: pneumonia, chronic obstructive cystic fibrosis, tuberculosis are generally caused by viruses, bacteria and fungi. As these infections are very difficult to treat, new therapeutic approaches are investigated in order to maximize the efficiency of the treatment and to reduce the major complications that can occur. The main objective of this study was focused on the preparation of drug-loaded peptides-functionalized microcapsules, obtained by a double emulsion, based on carboxylated chitosan (CMCS), poly(vinyl alcohol) (PVA) and an activator [4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride] (DMT-MM), for the dual active targeting and treatment of pulmonary infections. The microcapsules were functionalized on the surface with both CGSPGWVRC and indolicidin (IN) peptides, as effective ligands for the active targeting of both alveolar capillary endothelial cells and bacterial cells. FTIR spectroscopy confirmed the formation of ester and amide bonds into the structure of prepared microcapsules. Microcapsules diameter varied between 893 and 965 nm. The swelling degree in PBS, at pH 7.4, ranged between 1760 %- 2100 %. All the analyzed samples showed hemolysis degrees lower than 2 %, which demonstrated their non-hemolytic character. Evaluation of the impact of microcapsules on WI-38 normal human lung cells and RAW 264.7 mouse macrophages revealed a non-toxic or slightly cytotoxic effect. Internalization assay proved that microcapsules were localized at intracellular level.

Polyelectrolyte Microcapsules: An Extended Release System for the Antiarrhythmic Complex of Allapinin with Glycyrrhizic Acid Salt.

Allapinin has antiarrhythmic activity and can be used to prevent and treat various supraventricular and ventricular arrhythmias. Nevertheless, it is highly toxic and has a number of side effects associated with non-specific accumulation in various tissues. The complex of this substance with the monoammonium salt of glycyrrhizic acid (Al:MASGA) has less toxicity and improved antiarrhythmic activity. However, the encapsulation of Al:MASGA in polyelectrolyte microcapsules (PMC) for prolonged release will reduce the residual adverse effects of this drug. In this work, the possibility of encapsulating the allapinin-MASGA complex in polyelectrolyte microcapsules based on polyallylamine and polystyrene sulfonate was investigated. The encapsulation methods of the allapinin-MASGA in polyelectrolyte microcapsules by adsorption and coprecipitation were compared. It was found that the coprecipitation method did not result in the encapsulation of Al:MASGA. The sorption method facilitated the encapsulation of up to 80% of the original substance content in solution in PMC. The release of the encapsulated substance was further investigated, and it was shown that the release of the encapsulated Al:MASGA was independent of the substance content in the capsules, but at pH 5, a two-fold decrease in the rate of drug release was observed.

Multi-Stimuli-Responsive, Topology-Regulated, and Lignin-Based Nano/Microcapsules from Pickering Emulsion Templates for Bidirectional Delivery of Pesticides.

The increasing demand for improving pesticide utilization efficiency has prompted the development of sustainable, targeted, and stimuli-responsive delivery systems. Herein, a multi-stimuli-responsive nano/microcapsule bidirectional delivery system loaded with pyraclostrobin (Pyr) is prepared through interfacial cross-linking from a lignin-based Pickering emulsion template. During this process, methacrylated alkali lignin nanoparticles (LNPs) are utilized as stabilizers for the tunable oil-water (O/W) Pickering emulsion. Subsequently, a thiol-ene radical reaction occurs with the acid-labile cross-linkers at the oil-water interface, leading to the formation of lignin nano/microcapsules (LNCs) with various topological shapes. Through the investigation of the polymerization process and the structure of LNC, it was found that the amphiphilicity-driven diffusion and distribution of cyclohexanone impact the topology of LNC. The obtained Pyr@LNC exhibits high encapsulation efficiency, tunable size, and excellent UV shielding to Pyr. Additionally, the flexible topology of the Pyr@LNC shell enhances the retention and adhesion of the foliar surface. Furthermore, Pyr@LNC exhibits pH/laccase-responsive targeting against Botrytis disease, enabling the intelligent release of Pyr. The in vivo fungicidal activity shows that efficacy of Pyr@LNC is 53% ± 2% at 14 days postspraying, whereas the effectiveness of Pyr suspension concentrate is only 29% ± 4%, and the acute toxicity of Pyr@LNC to zebrafish is reduced by more than 9-fold compared with that of Pyr technical. Moreover, confocal laser scanning microscopy shows that the LNCs can be bidirectionally translocated in plants. Therefore, the topology-regulated bidirectional delivery system LNC has great practical potential for sustainable agriculture.

Dual Functional Microcapsule based on Monodisperse Short PEG Amphiphile for Drug Encapsulation and Protein Affinity Controlled Release.

A short monodisperse poly(ethylene glycol) (PEG) and a neutral organic rotamer conjugate TEG-BTA-2 amphiphile was designed for the construction of a stimuli-responsive switchable self-assembled structure for drug encapsulation by noncovalent interaction and targeted controlled delivery. A short PEG, tetraethylene glycol (TEG) was covalently attached with a neutral organic rotamer benzothiazole dye (BTA-2) affording the neutral TEG-BTA-2 (<500 D). The TEG-BTA-2 is self-assembled into a microsphere in an aqueous medium, but remarkably undergoes morphology change switching to a rice-like microcapsule for curcumin encapsulation. Curcumin-loaded microcapsules were stable in an aqueous solution, however, were noticed disintegrating upon the addition of BSA protein. This is possibly due to an interaction with BSA protein leading to a protein affinity-controlled curcumin release in a neutral PBS buffer. Moreover, cell internalization of the neutral amphiphile TEG-BTA-2 into A549 cells was observed by fluorescence microscopy, providing an opportunity for application as a molecular vehicle for targeted drug delivery and monitoring.

Encapsulation and characterization of soy protein-based ω-3 medium- and long- chain triacylglycerols microencapsulated with diverse homogenization techniques for improving oxidation stability.

Recently, MLCTs have attracted considerable attention as a potential alternative to traditional oils due to their suppressive effect on fat accumulation and insulin sensitivity. In this study, the microcapsules of MLCTs with superior performance were fabricated through different homogenization processes to overcome the limitations of ω-3 medium- and long- chain triacylglycerols (MLCTs), including poor stability and prone oxidation. Additionally, the impact of various homogenization techniques, namely, high-pressure, ultrasound, and cavitation jet, on the particle structure, encapsulation efficiency, and oxidation stability of microcapsules (MLCTs) was investigated. The MLCTs microcapsules fabricated through high-pressure homogenization had a smaller particle size of 295.12 nm, lower PDI of 0.24, and a higher zeta-potential absolute value of 32.65, which significantly improved their dispersion and encapsulation efficiency, reaching 94.56 % after the spray-drying process. Furthermore, the low moisture content and superior storage stability of MLCTs microcapsules have the potential to serve as carriers of liposoluble actives.

A Gas Therapy Strategy for Intestinal Flora Regulation and Colitis Treatment by Nanogel-Based Multistage NO Delivery Microcapsules.

Current approaches to treating inflammatory bowel disease focus on the suppression of overactive immune responses, the removal of reactive intestinal oxygen species, and regulation of the intestinal flora. However, owing to the complex structure of the gastrointestinal tract and the influence of mucus, current small-molecule and biologic-based drugs for treating colitis cannot effectively act at the site of colon inflammation, and as a result, they tend to exhibit low efficacies and toxic side effects. In this study, nanogel-based multistage NO delivery microcapsules are developed to achieve NO release at the inflammation site by targeting the inflammatory tissues using the nanogel. Surprisingly, oral administration of the microcapsules suppresses the growth of pathogenic bacteria and increases the abundance of probiotic bacteria. Metabolomics further show that an increased abundance of intestinal probiotics promotes the production of metabolites, including short-chain fatty acids and indole derivatives, which modulate the intestinal immunity and restore the intestinal barrier via the interleukin-17 and PI3K-Akt signaling pathways. This work reveals that the developed gas therapy strategy based on multistage NO delivery microcapsules modulates the intestinal microbial balance, thereby reducing inflammation and promoting intestinal barrier repair, ultimately providing a new therapeutic approach for the clinical management of colitis.

Preparation and characterisation of novel casein-gum Arabic composite microcapsules for targeted in vivo delivery of Lactiplantibacillus plantarum A3.

The health benefits of probiotics in the body are predicated on their ability to remain viable in harsh gastrointestinal conditions and complex pathological microenvironments. Casein and gum Arabic (GA), with dual emulsifying and stabilising effects in colloidal systems. Therefore, the objective of this research was to develop a novel microcapsule to encapsulate Lactiplantibacillus plantarum A3 using casein and GA as wall materials to improve the survival of the bacteria during gastrointestinal digestion, storage and lyophilization. The casein and GA composite microcapsules were prepared and characterised by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM). It was found that the microcapsules had stable morphology, uniform size and spherical shape. The results revealed that the encapsulation of microcapsules significantly improved the survival of L. plantarum A3 in gastrointestinal fluid environment (5.52 × 109 cfu/ml) and lyophilization treatment (6.25 × 109 cfu/ml). Furthermore, the microencapsulated L. plantarum A3 exhibited an improved ability to regulate intestinal microbiota by effectively increasing the relative abundance of Bacteroidetes, Proteobacteria and Actinobacteria and decreasing the relative abundance of Firmicutes in vivo. The findings of the study will help to design a lactic acid bacteria encapsulation system based on the gastrointestinal environment and provide a basis for the development of probiotic functional products.

Extemporaneous Compounding of Low-strength Aspirin Capsules for Desensitization Protocols.

Aspirin is a non-steroidal, anti-inflammatory drug used for a range of indications. For patients with aspirin hypersensitivities, a desensitization procedure may be prescribed, and the initial low doses of <81 mg need to be provided by compounded preparations. Compounding with aspirin is associated with stability challenges due to its poor chemical stability. Additionally, low-strength preparations often exhibit dosage accuracy and uniformity issues. This study was designed to assess the feasibility of compounding low-strength aspirin capsules for the use in desensitization protocols. Aspirin capsules of 40-mg, 10-mg, 3-mg, and 1-mg strengths were prepared by manual filling of dry powders. Formulations were kept as simple as possible for ease of compounding, and the ingredients and compounding procedures were carefully selected to minimize the moisture content and to optimize the dosage accuracy. For the 40-mg and 10-mg capsules, two formulations were tested, using pure drug or crushed tablet powder. For the 3-mg and 1-mg capsules, only one formulation was tested, using a 5% mixture of pure drug and cellulose. All formulations were filled into hydroxypropyl methylcellulose capsule shells and stored at room temperature for 90 days. A  stability indicating, high-performance liquid chromatography method was used to analyze the quality of the capsules. The initial potency results of all capsule formulations were within 100% to 105% of the label claim, and the standard deviation was <3% for all formulations except the 1-mg strength (7%). The use of crushed tablet powder over pure drug powder appeared to reduce the potency variability, probably due to the larger fill weight per capsule. Upon storage at room temperature, the 40-mg and 10-mg formulations retained >90% of the label claim for up to 90 days, but the 3-mg and 1-mg formulations retained >90% of the label claim for up to only 31 days. Low-strength aspirin capsules were prepared successfully by compounding with a beyond-use date of at least 31 days at room temperature. However, the overall trend confirmed the challenges of achieving dosage uniformity and aspirin stability at 3-mg and 1-mg strengths. For general application in compounding pharmacies, trial batches are recommended with proper analytical testing.

Smart Bactericidal Capsules Based on Cationic Luminescent Nanoclusters for Controllable Treatment of Drug-Resistant Bacterial Infection.

Effective treatment of drug-resistant bacteria infected wound has been a longstanding challenge for healthcare systems. In particular, the development of novel strategies for controllable delivery and smart release of antimicrobial agents is greatly demanded. Herein, the design of biodegradable microcapsules carrying bactericidal gold nanoclusters (AuNCs) as an attractive platform for the effective treatment of drug-resistant bacteria infective wounds is reported. AuNC capsules are fabricated via the well-controlled layer-by-layer strategy, which possess intrinsic near-infrared fluorescence and good biocompatibility. Importantly, these AuNC capsules exhibit strong, specific antibacterial activity toward both S. aureus and methicillin-resistant S. aureus (MRSA). Further mechanistic studies by fluorescence confocal imaging and inductively coupled plasma mass spectrometry reveal that these AuNC capsules will be degraded in the S. aureus environment rather than E. coli, which then controllably release the loaded cationic AuNCs to exert antibacterial effect. Consequently, these AuNC capsules show remarkable therapeutic effect for the MRSA infected wound on a mouse model, and intrinsic fluorescence property of AuNC capsules enables in situ visualization of wound dressings. This study suggests the great potential of microcapsule-based platform as smart carriers of bactericidal agents for the effective treatment of drug-resistant bacterial infection as well as other therapeutic purposes.