High Encapsulation Efficiency Research Articles

Targeting pentamidine towards CD44-overexpressing cells using hyaluronated lipid-polymer hybrid nanoparticles.

Biodegradable nanocarriers possess enormous potential for use as drug delivery systems that can accomplish controlled and targeted drug release, and a wide range of nanosystems have been reported for the treatment and/or diagnosis of various diseases and disorders. Of the various nanocarriers currently available, liposomes and polymer nanoparticles have been extensively studied and some formulations have already reached the market. However, a combination of properties to create a single hybrid system can give these carriers significant advantages, such as improvement in encapsulation efficacy, higher stability, and active targeting towards specific cells or tissues, over lipid or polymer-based platforms. To this aim, this work presents the formulation of poly(lactic-co-glycolic) acid (PLGA) nanoparticles in the presence of a hyaluronic acid (HA)-phospholipid conjugate (HA-DPPE), which was used to anchor HA onto the nanoparticle surface and therefore create an actively targeted hybrid nanosystem. Furthermore, ionic interactions have been proposed for drug encapsulation, leading us to select the free base form of pentamidine (PTM-B) as the model drug. We herein report the preparation of hybrid nanocarriers that were loaded via ion-pairing between the negatively charged PLGA and HA and the positively charged PTM-B, demonstrating an improved loading capacity compared to PLGA-based nanoparticles. The nanocarriers displayed a size of below 150nm, a negative zeta potential of -35mV, a core-shell internal arrangement and high encapsulation efficiency (90%). Finally, the ability to be taken up and exert preferential and receptor-mediated cytotoxicity on cancer cells that overexpress the HA specific receptor (CD44) has been evaluated. Competition assays supported the hypothesis that PLGA/HA-DPPE nanoparticles deliver their cargo within cells in a CD44-dependent manner.

Alginate/Carboxymethyl Chitosan Core-Shell Microspheres Coloaded with Doxorubicin/DocetaxelReverse Chemotherapy Resistance in Anaplastic Thyroid Carcinoma.

Drug resistance is a major obstacle in the treatment of anaplastic thyroid carcinoma (ATC) with the combination of docetaxel (DTX) and doxorubicin (DOX). Excessive intracellular drug efflux is considered a key factor contributing to drug resistance. Therefore, developing drug-loaded microspheres to enhance cellular uptake and inhibit efflux of docetaxel and doxorubicin may be an effective strategy to overcome chemoresistance. Alginate-Doxorubicin@carboxymethyl chitosan-Docetaxel (A-DOX@C-DTX) microspheres were prepared using an electrostatic spraying-assisted microfluidic device. The microspheres were characterized, and the in vitro drug release profiles and extracellular efflux rates were determined. The effects of A-DOX@C-DTX microspheres on drug-resistant ATC cells were evaluated in vitro. In vivo, a subcutaneous tumor model was established in mice to investigate the effects of A-DOX@C-DTX microspheres on tumor growth, as well as the accumulation and release of the materials at the tumor site. We successfully prepared ALG/CMC microspheres with a core-shell structure. These microspheres exhibited controllable size, good monodispersity, excellent biocompatibility, high encapsulation efficiency for doxorubicin and docetaxel, and high drug loading capacity. Moreover, the microspheres promoted cellular uptake of doxorubicin and docetaxel while inhibiting their efflux. A-DOX@C-DTX microspheres showed significant inhibition of viability, proliferation, migration, and invasion of drug-resistant ATC cells in vitro. In vivo, A-DOX@C-DTX microspheres suppressed tumor growth, induced tumor tissue necrosis, and promoted tumor cell apoptosis. Additionally, the microspheres facilitated the enrichment of active substances in the tumor and their sustained release. A-DOX@C-DTX microspheres exhibited superior anti-tumor effects compared to free drug treatment both in vitro and in vivo, particularly against drug-resistant ATC cells. This improved therapeutic efficacy may be attributed to the enhanced drug uptake and reduced drug efflux in drug-resistant ATC cells facilitated by ALG/CMC microspheres.

Preparation and characterization of artemether-loaded niosomes in Leishmania major-induced cutaneous leishmaniasis

Cutaneous leishmaniasis is the most prevalent form of leishmaniasis worldwide. Although various anti-leishmanial regimens have been considered, due to the lack of efficacy or occurrence of adverse reactions, design and development of novel topical delivery systems would be essential. This study aimed to prepare artemether (ART)-loaded niosomes and evaluate their anti-leishmanial effects against Leishmania major. ART-loaded niosomes were prepared through the thin-film hydration technique and characterized in terms of particle size, zeta potential, morphology, differential scanning calorimetry, drug loading, and drug release. Furthermore, anti-leishmanial effect of the preparation was assessed in vitro and in vivo. The prepared ART-loaded niosomes were spherical with an average diameter of about 100 and 300 nm with high encapsulation efficiencies of > 99%. The results of in vitro cytotoxicity revealed that ART-loaded niosomes had significantly higher anti-leishmanial activity, lower general toxicity, and higher selectivity index (SI). Half-maximal inhibitory concentration (IC50) values of ART, ART-loaded niosomes, and liposomal amphotericin B were 39.09, 15.12, and 20 µg/mL, respectively. Also, according to the in vivo study results, ART-loaded niosomes with an average size of 300 nm showed the highest anti-leishmanial effects in animal studies. ART-loaded niosomes would be promising topical drug delivery system for the management of cutaneous leishmaniasis.

Microencapsulation of purple tea polyphenols using the vibrating nozzle ionotropic gelation technology: Metabolomics, bioactivity, and application in milky tea

No research has been completed on the microencapsulation of purple tea extracts or on the use of such extracts in food models. Considering the worldwide importance of C. sinensis teas, this work aims to optimise the extraction of antioxidant polyphenols from purple tea leaves using a sustainable, green, ultrasonic-assisted extraction, and to design milky teas added with microcapsules produced by the vibrating nozzle ionotropic gelation method. A combination of 28 min, 495 W ultrasound power, and 50% ethanol were the ideal experimental conditions for obtaining the optimal extract (OPM). OPM displayed antioxidant activity and inhibited α-glucosidase (IC50=23.0±0.3 μg/mL) and α-amylase (IC50=12.4±0.9 mg/mL) in vitro. In human erythrocytes, OPM showed an in vitro antihaemolytic effect and decreased reactive oxygen species generation in a concentration-dependent manner. Also, OPM exhibited a protective effect against H2O2-treated astrocytes at 0.1 and 0.2 mg/mL. The microencapsulation of OPM extract resulting in a high encapsulation efficiency (84%), and milky teas added with OPM and microencapsulated OPM had higher antioxidant activity than the conventional counterpart.

Role of cyclodextrin inclusion complexes assembled in the fast-dissolving structures of electrospun gelatin mats to extend the release of menthol

In this study, inclusion complexes (ICs) of menthol with various cyclodextrins (CDs) [α-CD, β-CD, γ-CD, (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD), and methyl-β-cyclodextrin (M-β-CD)] were prepared first, and then the ICs with the highest encapsulation efficiency were applied in electrospun gelatin mats to extend release of menthol. Electrospinning feed solutions in terms of surface tension, zeta potential, electrical conductivity, and rheological properties were evaluated. The diameter and morphology of the pure gelatin and the CDs-loaded gelatin mats were analyzed using microscopy (FESEM and AFM), which confirms that CDs loading leads to a decrease in the diameter of the nanofibers. The longest disintegration time belonged to the gelatin mat containing the β-CD complex. Comparison of the FTIR spectrum and XRD patterns of gelatin mats containing menthol-loaded CD complexes with the pure compounds confirmed the successful encapsulation of menthol inside the cavity of the CD, and also the disappearance of the crystalline state of electrospun gelatin mats. Applying the electrospun gelatin mats as a fast-dissolving structure for the menthol-loaded inclusion complexes increased its thermal stability. In the bioadhesieve test, the lowest force required to separate the gelatin mat from the skin model was obtained in the menthol-containing β-CD gelatin mat (6.21± 1.01 g). The menthol release from the pure gelatin mats was much faster than the electrospun mats containing CDs complexes, however the menthol-loaded β-CD gelatin mat showed the slowest release into the simulated saliva. Peppas-Sahlin and Fickian diffusion (Case-I) were the best-fitted model and menthol release mechanism, respectively.

Enhanced In Vitro Antiviral Activity of Ivermectin-Loaded Nanostructured Lipid Carriers against Porcine Epidemic Diarrhea Virus via Improved Intracellular Delivery

Porcine epidemic diarrhea virus (PEDV) is an acute enteric coronavirus, inducing watery diarrhea and high mortality in piglets, leading to huge economic losses in global pig industry. Ivermectin (IVM), an FDA-approved antiparasitic agent, is characterized by high efficacy and wide applicability. However, the poor bioavailability limits its application. Since the virus is parasitized inside the host cells, increasing the intracellular drug uptake can improve antiviral efficacy. Hence, we aimed to develop nanostructured lipid carriers (NLCs) to enhance the antiviral efficacy of IVM. The findings first revealed the capacity of IVM to inhibit the infectivity of PEDV by reducing viral replication with a certain direct inactivation effect. The as-prepared IVM-NLCs possessed hydrodynamic diameter of 153.5 nm with a zeta potential of −31.5 mV and high encapsulation efficiency (95.72%) and drug loading (11.17%). IVM interacted with lipids and was enveloped in lipid carriers with an amorphous state. Furthermore, its encapsulation in NLCs could enhance drug internalization. Meanwhile, IVM-NLCs inhibited PEDV proliferation by up to three orders of magnitude in terms of viral RNA copies, impeding the accumulation of reactive oxygen species and mitigating the mitochondrial dysfunction caused by PEDV infection. Moreover, IVM-NLCs markedly decreased the apoptosis rate of PEDV-induced Vero cells. Hence, IVM-NLCs showed superior inhibitory effect against PEDV compared to free IVM. Together, these results implied that NLCs is an efficient delivery system for IVM to improve its antiviral efficacy against PEDV via enhanced intracellular uptake.

Characterization of Grape Pomace Extract Microcapsules: The Influence of Carbohydrate Co-Coating on the Stabilization of Goat Whey Protein as a Primary Coating

Both grape pomace and whey are waste products from the food industry that are rich in valuable ingredients. The utilization of these two by-products is becoming increasingly possible as consumer awareness of upcycling increases. The biological activities of grape pomace extract (GPE) are diverse and depend on its bioavailability, which is influenced by processes in the digestive system. In this work, goat whey protein (GW) was used as the primary coating to protect the phenolic compounds of GPE during the spray drying process. In addition, trehalose (T), sucrose (S), xylose (X), and maltodextrin (MD) were added to the goat whey proteins as co-coatings and protein stabilizers. All spray drying experiments resulted in microcapsules (MC) with a high encapsulation efficiency (77.6–95.5%) and yield (91.5–99.0%) and almost 100% recovery of phenolic compounds during the release test. For o-coumaric acid, the GW-coated microcapsules (MC) showed a bioavailability index of up to 731.23%. A semi-crystalline structure and hydrophilicity were characteristics of the MC coated with 10% T, S, X, or 5% MD. GW alone or in combination with T, S, MD, or X proved to be a promising carrier for polyphenols from grape pomace extract and ensured good bioavailability of these natural antioxidants.

Oral soluble shell prepared from OSA starch incorporated with tea polyphenols for the microencapsulation of Sichuan pepper oleoresin: Characterization, flavor stability, release mechanisms and its application in mooncake

The market share of Sichuan pepper oleoresin (SPO) in the flavor industry is increasing steadily; however, its high volatility, low water solubility, and poor stability continue to pose significant challenges to application. The microencapsulation prepared by emulsion embedding and spray drying is considered as an effective technique to solve the above problems. Sodium octenyl succinate starch (OSA starch) and tea polyphenols (TPs) were used to develop OSA-TPs complex as encapsulants for SPO to prepare orally soluble microcapsules. And the optimum doping of TPs was determined. SPO microcapsules have good properties with high encapsulation efficiency up to 88.13 ± 1.48% and high payload up to 41.58 ± 1.86% with low water content and high heat resistance. The binding mechanism of OSA starch with TPs and its regulation mechanism and effect on SPOs were further analyzed and clarified. The binding mechanism between OSA starch and TPs was clarified in further analyses. The OSA-TPs complexes enhanced the rehydration, release in food matrix and storage stability of SPO, and exhibited good sensory immediacy. Flavor-improved mooncakes were successfully developed, achieving the combination of mooncake flavor and SPO flavor. This study provided a valuable way to prepare flavoring microcapsules suitable for the catering industry, opened up the combined application of SPO and bakery ingredients, and was of great practical value and significance for improving the processing quality of flavor foods, driving the development of the SPO industry, and enhancing the national dietary experience.

Fabrication of polysaccharide-coated oleanolic acid-curcumin-coassembled nanoparticles (OA/Cur NPs): Enhancement of colloidal stability and water solubility

Natural terpenoid carriers, such as oleanolic acid (OA), can enhance the water solubility and stability of hydrophobic compounds such as curcumin (Cur). However, improving the colloidal stability of nanoparticle emulsions and resolving the redispersion problem of freeze-dried nanoparticle powders remain significant challenges. In this study, we fabricated coassembled oleanolic acid-curcumin nanoparticles (OA/Cur NPs) and applied a polysaccharide surface coating method to improve their colloidal stability and water solubility. The results showed that the optimal ratio of Cur/OA for preparing OA/Cur NPs was 4:10, resulting in a high encapsulation efficiency (EE) of Cur (75.2%). Additionally, TEM, contact angle tests, Turbiscan TOWER optical stability analysis of the polysaccharide-coated OA/Cur NP emulsions and redispersion tests of their lyophilized powders verified the advantages of carboxymethyl chitosan/β-cyclodextrin (CMC/β-CD) coating over other polysaccharides. This study indicated that polysaccharide coating is an effective method for enhancing the colloidal stability, water solubility, and redispersibility of OA/Cur NPs.

Development of intestine-targeted microcapsules for enhanced delivery of fucoxanthin: A strategy to mitigate lipid accumulation in vitro and in vivo

The development of intestine-targeted microcapsules using spray drying without maltodextrin is still a challenge. Herein, intestine-targeted fucoxanthin-loaded microcapsules (Fx-MIC) were developed using the spray drying method. The microcapsules were formed by homogenizing fucoxanthin/conjugated linoleic acid (Fx/CLA) and whey protein isolate/Arabic gum (WPI/AG) mixture, followed by spray drying without maltodextrin. The effect of the ratio of Fx/CLA to WPI/AG in Fx-MIC on their morphology and encapsulation efficiency was evaluated. An Fx/CLA-to-WPI/AG ratio of 1:3 yielded a uniform particle size and the highest encapsulation efficiency (91.11%). In vitro simulated digestion demonstrated that Fx-MIC effectively protected Fx from premature release in the stomach and exhibited a release efficiency of 66.08% in the intestine. The digestion product of Fx-MIC effectively inhibited 3T3-L1 cell differentiation and lipid accumulation, demonstrating its ability to reduce lipid accumulation in vitro. Moreover, in high-fat diet (HFD)-induced obesity mice, Fx-MIC exhibited significant reductions in body weight, liver weight, and fat mass. Additionally, Fx-MIC demonstrated notable effects on lowering blood lipid levels and mitigating liver damage. In conclusion, the use of Fx-MIC facilitated the targeted release of Fx, thereby enhancing its anti-obesity effects. This promising result suggests potential applications of Fx-MIC in the food industry.

Combinatorial Therapy: Targeting CD133+ Glioma Stem-like Cells with a Polysaccharide–Prodrug Complex Functionalised Gold Nanocages

Cancer treatments are advancing to harness the body’s immune system against tumours, aiming for lasting effects. This progress involves combining potent chemotherapy drugs with immunogens to kill cancer cells and trigger lasting immunity. Developing new prodrugs that integrate both chemotherapy and immune-boosting elements could significantly improve anticancer outcomes by activating multiple mechanisms to kill cancer cells. While bacterial polysaccharides are typically not used in therapy due to their immune-stimulating properties, we propose a safe application of an extremophilic bacterial polysaccharide, Mauran (MR), modified with the anticancer drug 5-fluorouracil (5FU) to create a novel prodrug. This obtained prodrug, chloracetyl-MR-5FU, is specifically targeted using gold nanocages to CD133+ glioma cells. Test results have shown a high encapsulation efficiency of the drug during the polysaccharide modification process; its anticancer activity was demonstrated in vitro and the release of the prodrug was demonstrated in ex vivo studies.

Ultrasonic synthesis of green lipid nanocarriers loaded with Scutellaria barbata extract: a sustainable approach for enhanced anticancer and antibacterial therapy.

Ultrasonic manufacturing has emerged as a promising eco-friendly approach to synthesize lipid-based nanocarriers for targeted drug delivery. This study presents the novel ultrasonic preparation of lipid nanocarriers loaded with Scutellaria barbata extract, repurposed for anticancer and antibacterial use. High-frequency ultrasonic waves enabled the precise self-assembly of DSPE-PEG, Span 40, and cholesterol to form nanocarriers encapsulating the therapeutic extract without the use of toxic solvents, exemplifying green nanotechnology. Leveraging the inherent anticancer and antibacterial properties of Scutellaria barbata, the study demonstrates that lipid encapsulation enhances the bioavailability and controlled release of the extract, which is vital for its therapeutic efficacy. Dynamic light scattering and transmission electron microscopy analyses confirmed the increase in size and successful encapsulation post-loading, along with an augmented negative zeta potential indicating enhanced stability. A high encapsulation efficiency of 91.93% was achieved, and in vitro assays revealed the loaded nanocarriers' optimized release kinetics and improved antimicrobial potency against Pseudomonas aeruginosa, compared to the free extract. The combination of ultrasonic synthesis and Scutellaria barbata in an eco-friendly manufacturing process not only advances green nanotechnology but also contributes to sustainable practices in pharmaceutical manufacturing. The data suggest that this innovative nanocarrier system could provide a robust platform for the development of nanotechnology-based therapeutics, enhancing drug delivery efficacy while aligning with environmental sustainability.

Encapsulation of black pepper oleoresin by applying different wall materials with spray- or freeze-drying techniques and quality determination

Black pepper oleoresin was processed to powder for handling convenience in logistics and applications. Various wall materials (gum Arabic, modified starch, maltodextrins, or blends of them) and drying techniques (spray drying or freeze drying) were applied. The main objective was to determine the proper method for producing black pepper oleoresin microcapsules. The results demonstrated that the suitable oleoresin concentration for feed emulsion formulation was 15% (w/w) concerning the wall material weight, while gum Arabic was deemed as the most suitable wall material of those investigated, based on feed emulsion stability and encapsulation efficiency. Freeze-drying had greater values for powder recovery and total piperine content; nonetheless, spray-drying was recommended, based on its higher encapsulation efficiency, product solubility, product stability during storage, and lower costs. Encapsulated oleoresin powders had a slower piperine retention percentage reduction than raw black pepper powder and free oleoresin during storage.

Engineering pH-sensitive dissolution of lipid-polymer nanoparticles by Eudragit integration impacts plasmid DNA (pDNA) transfection

Lipid-polymer nanoparticles offer a promising strategy for improving gene nanomedicines by combining the benefits of biocompatibility and stability associated with the individual systems. However, research to date has focused on poly-lactic-co-glycolic acid (PLGA) and resulted in inefficient transfection. In this study, biocompatible Eudragit constructs E100 and RS100 were formulated as lipid-polymer nanoparticles loaded with pDNA expressing red fluorescent protein (RFP) as a model therapeutic. Using a facile nanoprecipitation technique, a core–shell structure stabilised by lipid-polyethylene glycol (PEG) surfactant was produced and displayed resistance to ultracentrifugation. Both cationic polymers E100 (pH-sensitive dissolution at 5) and RS100 (pH-insensitive dissolution) produced 150–200 nm sized particles with a small positive surface charge (+3–5 mV) and high pDNA encapsulation efficiencies (EE) of 75–90%. The dissolution properties of the Eudragit polymers significantly impacted the biological performance in human embryonic kidney cells (HEK293T). Nanoparticles composed of polymer RS100 resulted in consistently high cell viability (80–100%), whereas polymer E100 demonstrated dose-dependent behaviour (20–90% cell viability). The low dissolution of polymer RS100 over the full pH range and the resulting nanoparticles failed to induce RFP expression in HEK293T cells. In contrast, polymer E100-constructed nanoparticles resulted in reproducible and gradually increasing RFP expression of 26–42% at 48–72 h. Intraperitoneal (IP) injection of the polymer E100-based nanoparticles in C57BL/6 mice resulted in targeted RFP expression in mouse testes with favourable biocompatibility one-week post-administration. These findings predicate Eudragit based lipid-polymer nanoparticles as a novel and effective carrier for nucleic acids, which could facilitate pre-clinical evaluation and translation of gene nanomedicines.

One Stone Several Birds: Self-Localizing Submicrocages With Dual Loading Points for Multifunctional Drug Delivery.

As the core index, how to improve bioavailability of loaded cargoes is a hot topic of drug carriers. In this study, aminated β-cyclodextrin (β-CD) as a cross-linking points is first integrated into 3D poly(acrylamide-co-acrylonitrile) (P(AAm-co-AN))network to build up a unique submicrocage (466.2 ± 47.6nm), featuring upper critical solution temperature (UCST; ≈40 °C), high volume expansion coefficient, and excellent biocompatibility. Hereinto, hydrophobic β-elemene (ELE)is locally loaded in β-CD with high loading efficiency (8.72%) and encapsulation efficiency (78.60%) through hydrophobic desolvation and host-guest interaction. Above UCST, the release of the loaded ELEis accelerated to 72.87% in 24 h, together with the enhanced sensitization effect of synergized radiotherapy. Given spontaneous long-lasting delivery, targeted embolization, and post-treatment removal of such UCST-type submicrocage, it is anticipated to provide a novel, facile, efficient, and versatile strategy of comprehensive anticancer treatments for high drug bioavailability.

Enhancing Stability and Antioxidant Activity of Resveratrol-Loaded Emulsions by Ovalbumin-Dextran Conjugates.

A reliable strategy for improving the stability and shelf life of protein-stabilized systems is by covalently attaching the protein onto a polysaccharide. In this study, ovalbumin (OVA) was modified with dextran (DEX) of different molecular weights by the Maillard reaction, and was used to enhance the stability of emulsions loaded with resveratrol. The surface hydrophobicity, thermal stability, and FT-IR spectroscopy of the OVA-DEX conjugates were evaluated. The results showed that the surface hydrophobicity of OVA decreased, while the thermal stability of OVA was significantly improved after DEX covalent modification. The OVA-DEX1k-stabilized emulsion exhibited high encapsulation efficiency of resveratrol, with the value of 89.0%. In addition, OVA-DEX was considerably more effective in droplet stabilization against different environmental stresses (heat, pH, and ionic strength). After 28 days of storage at 25 °C, the OVA-stabilized emulsion showed faster decomposition of resveratrol, whereas the OVA-DEX-conjugate-stabilized emulsion had approximately 73% retention of resveratrol. Moreover, the antioxidant activity of resveratrol-loaded emulsions stabilized by OVA-DEX was higher during storage under different temperatures. These results proved that the OVA-DEX conjugates had the potential to form stable, food-grade emulsion-based delivery systems against environmental stresses, which strongly supports their potential in the field of food and biomedical applications.

Facile fabrication of pesticide nanocapsules using cinnamaldehyde derived imide polymer as wall material for pH-responsive and ultraviolet shielding properties

The low utilization efficiency of pesticides poses a significant challenge to the sustainable development of agriculture. The nanocapsule-based pesticide delivery systems combine the advantages of nanotechnology and advanced materials to achieve on-demand and accurately targeted release. Herein, a facile and universal strategy was used to fabricate photosensitive pesticide nanocapsules using a versatile imine polymer derived from cinnamaldehyde (CIN) and ε-poly-L-lysine (PLL). Characterization results demonstrated that the nanocapsules prepared under optimal conditions exhibited uniform sizes (200–400 nm) and high encapsulation efficiency (>90 %). Photodegradation experiments revealed a significant increase of half-lives (7.21–55.57 times) under UV irradiation for the different pesticide nanocapsules. Furthermore, the pesticide nanocapsules demonstrated a high biological activity and excellent physicochemical properties, including pH-responsive release, maximum retention, and rain erosion resistance. The results of the mechanistic studies on the increased biological activity indicated that the nanocapsules could be adsorbed on the surface of target pathogenic cells and then released CIN and PLL, destroying the integrity of the cell membrane, and synergistically and effectively eradicating the pathogen with pesticide. Additionally, nanocapsules exhibited lower toxicity to zebrafish and genetic toxicity to Vicia faba than pesticide technical. Therefore, stimuli-responsive nanocapsules based on imide polymer have broad application prospects in the field of pesticides.

A carrier-free injectable hydrogel self-assembled using natural thymol and glycyrrhizin for MRSA-infected wound healing in rats

A carrier-free, self-assembled, injectable hydrogel was developed as wound dressing to deal with skin wound bleeding, bacterial infections, and wound healing. Natural thymol (THY) and glycyrrhizin were used to construct THY-loaded glycymicelles (THY@glycymicelles), which greatly improved the aqueous solubility of THY. Optimal THY@glycymicelles had a high encapsulation efficiency of THY and a uniform nanoparticle size. Interestingly, THY@glycymicelles could reversibly transform into THY@glycyrrhizin hydrogel (THY@glycygel) by adjusting neutral pH to skin pH (pH ∼ 4.9), and vice versa. THY@glycygel had a dense porous sponge microstructure and showed many excellent features, including injectable, hemostatic, antibacterial, and anti-inflammatory properties. In vitro antibacterial evaluation, THY@glycygel showed lower minimum inhibitory concentration to three tested bacteria than free THY. In terms of antibacterial mechanism, THY@glycygel could destroy the bacterial cell wall and membrane, increasing the extracellular alkaline phosphatase release, and inhibiting biofilm. THY@glycygel had strong hemostatic ability and exhibited great potential for antimicrobial activity and improving wound healing infected by methicillin-resistant Staphylococcus aureus (MRSA). Mechanisms including antimicrobial, promoting hair follicle growth, improving epidermis remolding and collagen deposition, decreasing inflammatory cytokine levels, and increasing growth factor levels promoted the MRSA-infected skin wound healing process of THY@glycygel. Totally, this novel hydrogel has great potential as wound dressing.

Liposomes to Cubosomes: The Evolution of Lipidic Nanocarriers and Their Cutting-Edge Biomedical Applications.

Lipidic nanoparticles have undergone extensive research toward the exploration of their diverse therapeutic applications. Although several liposomal formulations are in the clinic (e.g., DOXIL) for cancer therapy, there are many challenges associated with traditional liposomes. To address these issues, modifications in liposomal structure and further functionalization are desirable, leading to the emergence of solid lipid nanoparticles and the more recent liquid lipid nanoparticles. In this context, "cubosomes", third-generation lipidic nanocarriers, have attracted significant attention due to their numerous advantages, including their porous structure, structural adaptability, high encapsulation efficiency resulting from their extensive internal surface area, enhanced stability, and biocompatibility. Cubosomes offer the potential for both enhanced cellular uptake and controlled release of encapsulated payloads. Beyond cancer therapy, cubosomes have demonstrated effectiveness in wound healing, antibacterial treatments, and various dermatological applications. In this review, the authors provide an overview of the evolution of lipidic nanocarriers, spanning from conventional liposomes to solid lipid nanoparticles, with a special emphasis on the development and application of cubosomes. Additionally, it delves into recent applications and preclinical trials associated with cubosome formulations, which could be of significant interest to readers from backgrounds in nanomedicine and clinicians.

Bioprinting of a Liposomal Oxygen-Releasing Scaffold for Ovary Tissue Engineering.

This study addresses a critical challenge in bioprinting for regenerative medicine, specifically the issue of hypoxia compromising cell viability in engineered tissues. To overcome this hurdle, a novel approach using a microfluidic bioprinter is used to create a two-layer structure resembling the human ovary. This structure incorporates a liposomal oxygen-releasing system to enhance cell viability. The bioprinting technique enables the simultaneous extrusion of two distinct bioinks, namely, bioink A (comprising alginate 1% and 5 mg/mL PEGylated fibrinogen in a 20:1 molar ratio) and bioink B (containing alginate 0.5%). In addition, liposomal catalase and hydrogen peroxide (H2O2) are synthesized and incorporated into bioinks A and B, respectively. The liposomes are prepared using thin film hydration with a monodisperse size (140-160 nm) and high encapsulation efficiency. To assess construct functionality, isolated human ovarian cells are added to bioink A. The bioprinted constructs, with or without liposomal oxygen-releasing systems, are cultured under hypoxic and normoxic conditions for 3 days. Live/Dead assay results demonstrate that liposomal oxygen-releasing systems effectively preserve cell viability in hypoxic conditions, resembling viability under normoxic conditions without liposomes. PrestoBlue assay reveals significantly higher mitochondrial activity in constructs with liposomal oxygen delivery systems under both hypoxic and normoxic conditions. The evaluation of apoptosis status through annexin V immunostaining shows that liposomal oxygen-releasing scaffolds successfully protect cells from hypoxic stress, exhibiting a proportion of apoptotic cells similar to normoxic conditions. In contrast, constructs lacking liposomes in hypoxic conditions exhibit a higher incidence of cells in early-stage apoptosis. In conclusion, the study demonstrates the promising potential of bioprinted oxygen-releasing liposomal scaffolds to protect ovarian stromal cells in hypoxic environments. These innovative scaffolds not only offer protection but also recapitulate the mechanical differences between the medulla and the cortex in the normal ovary structure. This opens new avenues for advanced ovary tissue engineering and transplantation strategies.