Drug Release Research Articles

Dexamethasone-releasing PLGA films containing sucrose particles as porogens

The objective of this study was to investigate the use of sucrose particles as a porogen for preparing porous poly (lactide-co-glycolide) (PLGA) films containing dexamethasone by solvent casting technique to modulate PLGA degradation and drug release. Increasing the sucrose content up to 30 % decreased PLGA degradation and extended the drug release duration, a further increase to more than 60 % shortened the release duration. Sucrose created cavities and increased the internal pore surface area for the exchange of degraded acidic oligomers and monomers. This process decreased the autocatalysis within the PLGA matrix, resulting in slower drug release at lower sucrose content. At higher sucrose content, the interconnectivity of the PLGA matrix increased, accelerating the drug release of the entrapped drug. Decreasing the particle size of sucrose has a similar impact on PLGA degradation and drug release as increasing sucrose content. Smaller sucrose particles formed more cavities and a larger overall acidic exchange surface areas. Only 20% nanosized sucrose resulted in a quasi-linear release profile with interconnected sucrose particles, while 60% micronized or 100% non-micronized sucrose particles were necessary to achieve the same effect. In conclusion, modifying the content and particle size of sucrose effectively altered PLGA degradation and drug release, with nanosized sucrose being the most effective porogen. The data obtained with PLGA films could be potentially applied to other PLGA drug delivery systems such as microparticles or implants.

A biocompatible drug controlled release system based on β-cyclodextrin crosslinked magnetic lactose/ZIF-8 metal-organic frameworks for cancer treatment

Natural saccharides (Chitosan, Lactose, alginate, and β-cyclodextrin) have recently attracted much attention from researchers as drug delivery systems for cancer therapy. In this regard, for the first time, we designed a new targeted carrier based on magnetic lactose-modified ZIF-8 metal-organic frameworks crosslinked with β-cyclodextrin (M-Lactose@ZIF-8-β-CD) for the pH-responsive controlled release of anticancer drugs, hydrophilic doxorubicin (DOX), and hydrophobic curcumin (CUR) to MCF-7 breast cancer cells. The encapsulation efficiency of M-Lactose@ZIF-8-β-CD was found to be 95.16% for DOX and 65.01% for CUR. The in vitro release studies showed a pH-responsive controlled release of DOX and CUR from M-Lactose@ZIF-8-β-CD at pH 5, which confirmed the performance of the prepared carrier in the cancerous microenvironments. The release mechanism of both drugs was well described by the Korsmeyer-Peppas and Fickian diffusion. In addition, in vitro cytotoxicity, hemolysis, and antioxidant investigations clearly showed that the prepared M-Lactose@ZIF-8-β-CD carriers had good biocompatibility, high blood compatibility, and excellent antioxidant activity due to the presence of natural saccharides in carriers. Based on these findings, the M-Lactose@ZIF-8-β-CD can be applied as a promising targeted co-drug delivery carrier for cancer therapy.

Improved Transdermal Delivery of Anti-hypertensive Drug Loaded Nanostructured Lipid Carriers: Statistical Design, Optimization, Depiction and Pharmacokinetic Assessment

Background: The vasoselective calcium-channel blocker lercanidipine hydrochloride (LCH) is poorly absorbed orally (only 10% bioavailability) owing to its low solubility and hepatic metabolism. Because of the LCH's poor solubility and permeability, bioavailability is low and very variable, stable aqueous liquid formulations are challenging to create, and a uniform distribution of the medication is almost impossible to produce. Objective: The purpose of this research was to see whether an approach involving the development of nanostructured lipid carriers (NLCs) might be used to create an effective, innovative oral formulation of LCH. The efficacy of several synthetic and natural liquid lipids was compared using a hot homogenization-ultrasonication strategy. Methods: Following initial improvements with hot homogenization and ultrasonication, the LCHloaded NLCs formulation was fine-tuned by Box-Behnken statistical analysis. The optimal LCHNLCs composition includes the lipid phase (2-4% w/v) of stearic acid and oleic acid, the surfactants poloxamer 188 (1%) and Tween 80(1%), and other ingredients. Results: The optimized NLCs formulation was found to have mean vesicle sizes of 128.72 ± 1.59 nm, polydispersity indices of 0.169 ± 0.06, zeta potentials of -36.81 ± 0.42 mV, and entrapment efficiencies of 79.84 ± 0.11%. The optimized NLCs formulation released much more LCH (88.74 ± 4.62) than the LCH-suspension (36.84 ± 0.37%) in in-vitro drug release experiments lasting up to 24 hours. Ex vivo studies on the ability of LCH-NLCs to pass through the gut showed that drug permeation was much better than it was with plain LCH-solution. The in vivo pharmacodynamic analysis demonstrated that, compared to conventional LCH-suspension, NLCs released LCH more slowly and steadily over a longer time period. Conclusion: These findings provide additional evidence that NLCs have great promise as a drug delivery technology for the treatment of hypertension, just as they show promise as a controlled release formulation for the treatment of LCH.

Assessing the Efficacy of Berberine Hydrochloride-loaded Transethosomal Gel System in Treating Dermatophytosis Caused by Trichophyton rubrum in ex-vivo, in-vitro and in-vivo Models.

Dermatophytosis is the most common dermatological disorder worldwide. Many drugs are available in the market for the treatment of dermatophytosis, but they have had limited success due to the stratum corneum barrier, antifungal resistance, drug permeation, drug retention in skin layers, etc. Thus, there is a constant need for new topical compounds that are effective against dermatophytosis. Berberine-hydrochloride is an attractive candidate to become an antifungal drug, and by using nanotechnology, it achieves deeper penetration in skin layers with enhanced permeability through the stratum corneum. In this study, we developed an oleic acid-containing berberine-hydrochloride-loaded transethosomal gel for effective treatment of dermatophytosis by Trichophyton rubrum. Berberine- hydrochloride-loaded transethosomal gels were fabricated using the hot homogenization method, followed by the incorporation of transethosomes into the gel-based system using carbopol 934. Transethosomal gel was characterized by physicochemical properties, in vitro drug release, ex-vivo permeation studies, CLSM visualization, antifungal activity, histopathological evaluation, and dermatokinetic study. Berberine-hydrochloride-loaded transethosomes seemed to be spherical and found in a range between 200-300 nm. Berberine-hydrochloride-loaded transethosomal gel formulation also exhibited controlled ex-vivo permeation of berberine-hydrochloride over 24 hr through excised rat skin, and CLSM confirmed deeper penetration into skin layers. The in vivo study revealed that transethosomal gel had a healing effect on the skin of Wistar rats infected with Trichophyton rubrum and was better than luliconazole cream. The histopathological evaluation confirmed its safety, and the dermatokinetic study showed transethosomal gel superiority over marketed cream. Therefore, the incorporation of berberine hydrochloride-loaded transethosomal nanosystems into the gel has the potential to enhance antifungal activity and permeation through transdermal drug delivery.

Formulation and Optimization of Solid Lipid Nanoparticle-based Gel for Dermal Delivery of Linezolid Using Taguchi Design.

Linezolid (LNZ) is a synthetic oxazolidinone antibiotic approved for the treatment of uncomplicated and complicated skin and soft tissue infections caused by gram-positive bacteria. Typically, LNZ is administered orally or intravenously in most cases. However, prolonged therapy is associated with various side effects and life threatening complications. Cutaneous application of LNZ will assist in reducing the dose, hence minimizing the unwanted side/adverse effects associated with oral administration. Dermal delivery provides an alternative route of administration, facilitating a local and sustained concentration of the antimicrobial at the site of infection. The current research work aimed to formulate solid lipid nanoparticles (SLNs) based gel for dermal delivery of LNZ in the management of uncomplicated skin and soft tissue infections to maximise its benefits and minimise the side effects. SLNs were prepared by high-shear homogenisation and ultrasound method using Dynasan 114 as solid lipid and Pluronic F-68 as surfactant. The effect of surfactant concentration, drug-to-lipid ratio, and sonication time was investigated on particle size, zeta potential, and entrapment efficiency using the Taguchi design. The main effect plot of means and signal-to-noise ratio were generated to determine the optimized formulation. The optimized batch was formulated into a gel, and ex-vivo permeation study, in-vitro and in-vivo antibacterial activity were conducted. The optimised process parameters to achieve results were 2% surfactant concentration, a drug-to-lipid ratio of 1:2, and 360 s of sonication time. The optimized batch was 206.3± 0.17nm in size with a surface charge of -24.4± 4.67mV and entrapment efficiency of 80.90 ± 0.45%. SLN-based gel demonstrated anomalous transport with an 85.43% in vitro drug release. The gel showed a 5 cm zone of inhibition while evaluated for in vitro antibacterial activity against Staphylococcus aureus. Ex-vivo skin permeation studies demonstrated 20.308% drug permeation and 54.96% cutaneous deposition. In-vivo results showed a significant reduction in colony-forming units in the group treated with LNZ SLN-based gel. Ex-vivo studies ascertain the presence of the drug at the desired site and improve therapy. In-vivo results demonstrated the ability of SLN-based gel to significantly reduce the number of bacteria in the stripped infection model. The utilization of SLN as an LNZ carrier holds significant promise in dermal delivery.

Application of Box-Behnken design in the optimization and development of albendazole-loaded zein nanoparticles as a drug repurposing approach for colorectal cancer management

Colorectal cancer (CRC) is the second cancer worldwide representing a major global health challenge. Numerous effective anticancer drugs have been developed in the last decade, yet the problem remains due to their low therapeutic index and nonspecificity. A new anticancer therapeutic paradigm is based on repurposing and nanoformulating drugs. Albendazole (ALB), a popular anthelmintic agent, was recently repurposed against CRC cells. In this study zein, an amphiphilic protein, was used to formulate nanoparticles (NPs) loaded with ALB. Box-Behnken design was selected to optimize the loaded NPs, the concentrations of polyvinyl alcohol, acetic acid, and the weight of zein were the independent variables. The dependent variables were the particle size, polydispersity index, and zeta potential. The optimized formula displayed a size of 84.3 ± 0.41 nm, PDI 0.13 ± 0.012, and a zeta potential of 42.5 ± 2.35 mV. ALB was successfully encapsulated into zein NPs and the release study revealed a desirable pH-responsive drug release behavior, that was negligible discharge during the first 2 h at pH 1.2 and progressive in the simulated colon environment reaching 71.1 ± 0.34 % at 6 h and 92.4 ± 1.11 % at 24 h. The anticancer effect of the loaded NPs on the human HCT116 cells showed favorable effects at 1 μM concentrations with a significant decrease in the IC50 at days 2 and 3 upon loading albendazole into zein NPs. ZNPs proved to be prospective nanocarriers that could be used for the delivery of repurposed drugs in CRC treatment.

Development of puerarin-loaded poly(lactic acid) microspheres for sustained ocular delivery: In vitro/vivo evaluation

Diabetic retinopathy, an ocular complication of diabetes, is an important cause of blindness in adults. Puerarin is considered to have promising potential for clinical use in treating diabetic retinopathy. In this study, we designed a novel puerarin-loaded poly(lactic acid) sustained-release microspheres suitable for ocular administration, and we assessed itsin vitro and in vivo properties. The preparation of puerarin-loaded microspheres was optimized by Box-Behnken response surface design. The encapsulation efficiency and drug loading of microspheres were 35.71% and 3.85%, respectively. The microspheres exhibited good dispersion and high safety, making it suitable for ocular drug delivery. In vitro release demonstrated that microspheres had a well-sustained release effectiveness, and its release behavior complied with the zero-order kinetic characteristics. The results of ocular tissue distribution revealed that the CmaxandAUC0-∞ of the microspheres group in the retina and choroid were considerably higher than those of the solution group and the intravenous injection group. This research revealed that intravitreal injection of microspheres can significantly prolong the half-life of puerarin in eye tissues and achieve sustained drug release. Therefore, intravitreal injection of microspheres has positive implications for the treatment of diabetic retinopathy.

Development and evaluation of mucoadhesive buccal films for the sustained release of diclofenac sodium: An innovative approach for pain management

The research explores the development and evaluation of mucoadhesive buccal films for the sustained release of diclofenac sodium, a widely used non-steroidal anti-inflammatory drug (NSAID) for pain relief. Mucoadhesive buccal films are an innovative drug delivery system designed to adhere to the mucous membrane in the oral cavity, enabling the controlled release of drugs directly into the bloodstream, bypassing first-pass metabolism and improving therapeutic outcomes. These films provide sustained release, localized action, and improved compliance, making them more convenient for patients. Mucus membranes, which are moist surfaces lining body cavities, are the main components of mucus gels. The wetting theory applies to mucoadhesion, which involves the release of mucus from the mucosal surface into the bloodstream. The study aims to develop a more efficient and effective method for the controlled release of diclofenac sodium, a potent anti-inflammatory and analgesic drug.

МАРКЕТИНГОВЫЙ АНАЛИЗ АССОРТИМЕНТА ОСНОВНЫХ МОНОПРЕПАРАТОВ, ПРИМЕНЯЕМЫХ ДЛЯ ТЕРАПИИ РАССТРОЙСТВ СНА

In recent years, many studies have noted that the number of occurrence of various sleep disorders is increasing among the population, while such problems as self-medication, untimely access to a doctor, the presence of concomitant diseases, the development of acute forms of disorders into chronic ones are highlighted, all this affects the quality and life expectancy of the population and makes it relevant to study pharmacotherapy of drugs for the treatment of these disorders in the field of pharmaceutical care [1-6; 11]. The purpose of the study was to establish a list and conduct a marketing analysis of the assortment of the main groups of monopreparations used for the treatment of sleep disorders presented on the domestic pharmaceutical market for their subsequent use in more extensive comprehensive marketing research in the context of sleep disorder therapy. The materials for the study were data from the State Register of Medicines and regulatory documents reflecting the attitude of objects to accounting and control of their sale on the market. The following methods were used: comparisons, systematization, grouping, statistics, as well as structural and assortment analyses. The article presents the results of a study of the Russian market of monopreparations of this orientation. The systematization of the main monopreparations was carried out, as a result, 7 groups were identified, which include 25 international nonproprietary names of medicines represented by 78 trade names, the proportion of manufactured drugs within each group and relative to the total number of trade names were calculated. The next step was to analyze the conditions for the release of drugs, their inclusion in lists reflecting accounting and control during implementation in accordance with regulatory documentation. In conclusion, it is noted that the obtained ranking data and the corresponding calculations will serve as a basis for further research in the field of the pharmaceutical market of drugs used for sleep disorders.

Oral mucoadhesive drug delivery system: Formulation strategies and evaluation techniques

Mucoadhesive drug delivery systems (MDDS) represent an innovative method for administering drugs through oral routes such as the buccal, sublingual, and gingival areas. These systems leverage natural or synthetic polymers to ensure prolonged adherence to mucosal surfaces, enabling extended and controlled release of medication. Several factors influence the effectiveness of mucoadhesion, including the hydrophilicity of polymers, molecular weight, and environmental factors like pH and moisture levels. MDDS can take various forms, including tablets, films, patches, lozenges, and gels, each offering different drug release profiles such as immediate, sustained, or controlled. These systems enhance drug bioavailability by avoiding first-pass metabolism, making them particularly beneficial for medications with low oral bioavailability or those requiring targeted delivery. Although MDDS offer improved patient compliance and therapeutic effectiveness, they still face challenges like irritation, taste concerns, and the diluting effect of saliva, which can impact drug stability. Despite these challenges, MDDS hold significant promise for advancing drug delivery technologies across various medical applications. This review thoroughly examines the mechanisms, advantages, limitations, and future prospects of mucoadhesive drug delivery systems.

Multifunctional Analgesic Sutures from Microfluidic Spinning Technology.

Sutures are the most commonly used wound repair method after surgery. However, addressing delayed recovery and pain management remains a significant challenge. Here, microfibers are developed from microfluidic spinning with long-lasting analgesia capabilities for sutures. By using a solvent extraction manner, the polycaprolactone (PCL) microfibers encapsulated with ropivacaine (ROP), a well-known analgesic, can be continuously obtained from microfluidics. The intrinsic property of PCL and the advantage of microfluidic spinning technique impart the microfiber with highly controlled morphologies, mechanical strengths, as well as drug release. After exploring their biocompatibility both at in vitro and in vivo levels, the microfibers are directly applied to wound suture. The results demonstrate the lasting analgesic effect of the microfiber on mice with incision pain, highlighting its potential as promising suture for post-surgery treatments. It is anticipated that the multifunctional analgesic sutures produced through microfluidic spinning will pave the way for utilizing fibers as effective sutures in clinical incision wound treatment.

Microneedles as an Emerging Platform for Transdermal Delivery of Phytochemicals.

Phytochemicals, which are predominantly found in plants, hold substantial medicinal value. Despite their potential, challenges such as poor oral bioavailability and instability in the gastrointestinal tract have limited their therapeutic use. Traditional intra/transdermal drug delivery systems offer some advantages over oral administration but still suffer from issues such as limited penetration depth, slow drug release rates, and inconsistent drug absorption. In contrast, microneedles (MNs) represent a significant advancement in intra/transdermal drug delivery by providing precise control over phytochemical delivery and enhanced penetration capabilities. By circumventing skin barriers, MNs directly access dermal layers rich in blood vessels and lymphatics, thus facilitating efficient phytochemical delivery. This review extensively discusses the obstacles of traditional oral delivery and the benefits of intra/transdermal delivery routes with a particular focus on the transformative potential of MNs for phytochemical delivery. This review explores the complexities of delivering phytochemicals through intra/transdermal routes, the development and types of MNs as innovative delivery tools, and the optimal design and properties of MNs for effective phytochemical delivery. Additionally, this review examines the versatile applications of MN-mediated phytochemical delivery, including its role in administering phytophotosensitizers for photodynamic therapy, and concludes with insights into relevant patents and future perspectives.

Innovative Long-Acting Bisoprolol Patch: Synergistic Ion-Pair Skin Adsorption for Drug Delivery Control Coupled with Dynamic Modulation of Penetration Enhancers.

This study aims to develop a sustained release patch for bisoprolol (BSP) to address the issue of blood pressure fluctuations caused by traditional dosing methods, ensuring continuous drug release and efficient utilization. Long-chain saturated fatty acids (C6-C12) were chosen as counterions to precisely control BSP's permeation rate in the patch formulation, and the ion-pairing strategy's mechanism in drug delivery was thoroughly investigated. Molecular docking results revealed significant differences in the adsorption capacities of different ion pairs in the stratum corneum (SC) and epidermis, directly influencing their residence times and thereby regulating BSP's passive diffusion rate. Particularly, the BSP-C10 ion pair successfully reduced BSP's permeation rate to one-third of its baseline. To enhance drug delivery efficiency and reduce costs, chemical permeation enhancers (CPEs) are typically added to sustained release patches. In contrast to traditional static analyses based on cumulative permeation, this study utilized ATR-FTIR dynamic detection of isopropyl myristate (IPM) as a preferred enhancer, studying its disruptive effects on the skin barrier during drug delivery. The study observed that during drug delivery, the interaction between IPM and skin lipids follows a U-shaped trend: initially increasing, then decreasing, with the peak occurring at 10 h. Similarly, the drug delivery rate displays a comparable pattern. The addition of IPM as CPE increased the patch utilization rate from 39.8 ± 4.31 to 79.8 ± 7.27%. This strategy aims to rapidly reduce blood pressure in the initial phase with subsequent weakening of IPM disruption, allowing the ion-pairing strategy to dominate drug delivery control and maintain stable long-term therapeutic effects. Pharmacokinetic studies demonstrated that the newly developed BSP sustained release patch maintains stable blood drug concentrations, reduces burst release effects, increases bioavailability to 84.679%, doubles MRT0-t, halves Cmax, and significantly reduces the occurrence of blood pressure fluctuations.

Size effect of ZIF-8 based nanocarrier pesticide delivery system on targeted release and insecticidal activity.

Traditional chemical pesticides are easily lost by surface runoff and only small quantities reach the target, thus causing serious environmental pollution. In this work, dinotefuran@zeolitic imidazolate framework-8@polydopamine@zein (DNF@ZIF-8@PDA@zein), was constructed to deliver DNF with pH and enzyme double response of release, thereby achieving targeted release and efficient long-term pest control. DNF@ZIF-8@PDA@zein was synthesized with three hydrated diameters (249.73 ± 9.99 nm, 142.94 ± 5.63 nm and 75.16 ± 4.66 nm, respectively). The release of DNF from DNF@ZIF-8@PDA@zein after 28 h was significantly higher at pH 5.0 (89.22 ± 7.18%) compared to that at pH 8 (81.8 ± 6.11%). Protease-assisted release of DNF was notably higher than that without protease (pH 5: 89.22 ± 5.55% versus 27.19 ± 3.22%; pH 8: 81.8 ± 6.11% versus 25.39 ± 3.87%). The stimuli-responsive release of DNF from DNF@ZIF-8@PDA@zein increased with decreased particle size due to increased pore size, reduced binding forces (i.e., weaker π-π stacking, hydrogen bonding, and Zn-N covalent bonding), and the shortening of diffusion path, leading to faster disintegration and drug release. Additionally, the anti-photolysis ability of DNF@ZIF-8@PDA@zein was 3.2 times that of pure DNF. The insecticidal activity improved with smaller nanoparticles due to higher drug release rate and greater inhibition of detoxification enzyme activity by more zinc ion (Zn2+) dissolution. The pH and enzyme dual-responsive release as well as insecticidal activity of DNF@ZIF-8@PDA@zein increase with decreased nanoparticle size, showing effective pest management in long-term and potential application prospects in sustainable agriculture. © 2024 Society of Chemical Industry.

Low-cost fabrication of digital light processing 3D printed conical microneedles for biomedical applications

The 3D printing of microneedles has become an emerging area of research focus due to its ability to rapidly create microneedle arrays with parametrically variable geometry and composition. Through direct fabrication or via replica molding, 3D printed microneedles can facilitate iterative array assessment and act as a screening tool to quickly establish optimal parameters for tissue insertion and capacity for biomarker monitoring or drug release. However, the widespread adoption of 3D printing by microneedle array researcher group faces multiple barriers: (1) Investment in 3D printing systems that are traditionally associated with high-resolution pose a significant financial cost, (2) Current high-resolution printing methods are often slow and not conducive to rapid manufacturing, (3) Material selection can be limited in some ‘proprietary’ 3D printing systems (e.g. CLIP, SLA, or 2PP), (4) Given the multidisciplinary nature of the microneedle-field, researchers may not have the expertise to optimize printing parameters for a given material or printer. This work explores how ultra-low-cost digital light processing (DLP) printers can rapidly produce functional microneedle arrays for a variety of purposes, whether direct print, master mold production, or creation of coated microneedles, at a fraction of the cost of currently used systems. Further, this work highlights that high quality microneedle arrays can be created using DLP printing methods with reliability exceeding 98 %, tip radii on the order of 30 µm, and with appropriate parameter input optimization, high quality microneedle arrays can be fabricated that express desirable characteristics for multiple forms of solid microneedle array production.

Macrophage Membrane-Coated Nanoparticles for the Delivery of Natamycin Exhibit Increased Antifungal and Anti-Inflammatory Activities in Fungal Keratitis.

This study aims to explore the efficacy and safety of macrophage membrane-coated nanoparticles for the delivery of natamycin (NAT) in the therapy of fungal keratitis (FK). Macrophage membranes were isolated and identified by immunofluorescence staining (IFS). NAT was encapsulated into poly(lactic-co-glycolic acid) (PLGA). Fungal stimulated macrophage membranes (M1) or unstimulated membranes (M) were separately mixed and sonicated with PLGA nanoparticles. The biocompatible nanoparticles (PLGA-NAT, PLGA-NAT@M, and PLGA-NAT@M1) were characterized with zeta-sizer analysis, transmission electron microscopy (TEM), and Western blot. Drug encapsulation and loading efficiency and the release of NAT in the nanoparticles were detected by ultraviolet spectrophotometry. The cytotoxicity, ocular surface toxicity and irritability, and systemic safety of nanoparticles with different concentrations were assessed. In vitro, we examined the antifungal properties of the nanoparticles. The eye surface retention time, drug release, and curative effects on FK were evaluated in vitro and in vivo. IFS results showed the separation of the macrophage membrane and nucleus. The prepared nanoparticles had a typical "core-shell" structure and uniform nanometer size, and the membrane proteins were retained on the membrane allowing to exert functional effects of macrophage. The loading efficiencies of PLGA-NAT@M and PLGA-NAT@M1 were 7.6 and 6.7%, respectively. The encapsulation efficiencies of PLGA-NAT@M and PLGA-NAT@M1 were 51.2 and 41.5%, respectively. PLGA-NAT@M and PLGA-NAT@M1 could gradually release NAT and reduce the clearance of the ocular surface. Macrophage membranes enhanced the antifungal activity of PLGA-NAT. Furthermore, the membrane coated with macrophage increased the biocompatibility and decreased the corneal toxicity of nanoparticles. In vivo, PLGA-NAT@M1 significantly alleviated the severity of FK. In vitro, PLGA@M and PLGA@M1 reduced the protein levels of inflammatory cytokines after fungal stimulation. The prepared PLGA-NAT@M1 has good physical properties and biosafety. It could evade ocular surface clearance, release NAT gradually, and achieve high antifungal and anti-inflammatory efficiencies to FK. Macrophage membrane-coated nanoparticles clinically have high application potential to the treatment of FK.

Ferric Ions Crosslinked Hyaluronic Acid Beads: Potentials for Drug Delivery Use

ABSTRACT Introduction and purpose: Despite the attractive properties of hyaluronic acid (HA), The preparation of HA beads is still challenging. This article reports the preparation of pH-sensitive gel HA beads. The ionic gelation method was used to prepare the HA gel beads using ferric ions. This cross-linking type is based on forming coordination bonds, which enhance the mechanical properties of the prepared beads. Methods: The developed beads were characterized using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Scanning electron microscopy (SEM) examined the bead's morphology. Furthermore, the potential of HA gel beads as an oral drug delivery system was investigated using metformin as a hydrophilic model drug. The entrapment efficiency and in vitro, release, and release kinetics were evaluated. The crosslinking density and HA concentration effect on drug release and bead swelling capacity under pH 1.2 and 7.4 were also investigated. Results: The entrapment efficiency of metformin in HA beads was found to be 79.56 ± 3.89%. FTIR analysis indicated the ionic interaction between ferric ions and the carboxylic groups on the HA molecule. At the same time, there was no substantial interaction between metformin and the polymeric bead. Morphological evaluation and DSC analysis suggested the successful incorporation of metformin within the beads. The in vitro drug release evaluation showed pH-dependent extended release where the release kinetics followed the first-order mathematical model. Conclusions: This study provides a value-added formulation with the potential for drug delivery use, which can be further investigated for biomedical applications.

Machine learning-guided synthesis of nanomaterials for breast cancer therapy

Breast cancer is a common malignant tumor, which mostly occurs in female population and is caused by excessive proliferation of breast epithelial cells. Breast cancer can cause nipple discharge, breast lumps and other symptoms, but these symptoms lack certain specificity and are easily confused with other diseases, thus affecting the early treatment of the disease. Once the tumor progresses to the advanced stage, distant metastasis can occur, leading to dysfunction of the affected organs, and even threatening the patients’ lives. In this study, we synthesized high drug-loading gel particles and applied them to control the release of insoluble drugs. This method is simple to prepare, cost-effective, and validates their potential in breast cancer therapy. We first characterized the morphology and physicochemical properties of gel loaded with newly synthesized compound 1 by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), and thermal gravimetric analysis (TGA). Using newly synthesized insoluble compound 1 as a model drug, its efficacy in treating breast cancer was investigated. The results showed that hydrogel@compound 1 was able to significantly inhibit the proliferation, migration and invasion of breast cancer cells. Additionally, we utilized machine learning to screen three structurally similar compounds, which showed promising therapeutic effects, providing a new approach for the development of novel small-molecule drugs.

Preparation and Characterization of Cellulose/Silk Fibroin Composite Microparticles for Drug-Controlled Release Applications

Microparticles derived from biomaterials are becoming increasingly popular for application in drug delivery systems. In this study, the water-in-oil (W/O) emulsification–diffusion method was used to create cellulose (C), silk fibroin (SF), and C/SF composite microparticles. We then observed the morphology of all obtained microparticles using scanning electron microscopy (SEM), evaluated their functional groups using attenuated total reflection–Fourier transform infrared spectroscopy (ATR-FTIR), and conducted thermogravimetric analysis using a thermogravimetric analyzer (TGA). SEM micrographs indicated that the native SF microparticles have the highest spherical shape with smooth surfaces. With blue dextran, the C microparticle was smaller than the native microparticle, while the drug-loaded SF microparticles were larger than the native microparticle. The morphological surfaces of the C/SF composite microparticles were varied in shape and surface depending on the C/SF ratio used. The spherical shape of the C/SF composite microparticle increased as the SF content increased. Furthermore, the size of the drug-loaded C/SF composite microparticles increased when the SF content gradually increased. The significant functional groups in the C and SF structures were identified based on the ATR-FTIR data, and a suggestion was made regarding the interaction between the functional groups of each polymer. When compared to both native polymers, the C/SF composite microparticles exhibit improved thermal stability. XRD patterns indicated that all prepared particles have crystalline structures and are directly affected by the released profile. The C/SF composite microparticle at a 1:3 ratio had the lowest drug release content, whereas the hydrophilicity of the C microparticle affected the highest drug release content. As a result, one crucial factor affecting the medication released from the microparticle is its structure stability. According to the obtained results, C, SF, and C/SF composite microparticles show promise as delivery systems for drugs with controlled release.

Development of Stable and Intensified Mixing Processes for the Precise and Scalable Production of Uniform Drug Delivery Nanocarriers.

Nanocarriers show great promise in drug delivery but face challenges in stability, uniformity, and morphology control. This work introduces an enhanced mixing process to overcome these obstacles, specifically aiming to produce consistently sized poly(lactic-co-glycolic) acid (PLGA) nanoparticles loaded with anti-tumor drugs. By innovatively integrating a pulsation dampener into the microfluidic channels of a continuous flow preparation system, the flow stability of piston pumps is improved nearly tenfold. Consequently, large-scale production of uniformly sized nanoparticles with customizable dimensions is achieved through nanoprecipitation. Furthermore, incorporating terminal double-bond-functionalized poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-maleimide (PLGA-PEG-Mal) enables these nanoparticles to act as nano-crosslinkers. This facilitates in situ crosslinking with thiolated hyaluronic acid via a spontaneous thiol-ene coupling reaction under physiological conditions, allowing for minimally invasive drug administration and significantly enhancing localized drug retention. The material's degradability in the presence of endogenous enzymes ensures controlled drug release, as demonstrated with the anti-tumor drug doxorubicin (DOX). Validation in a murine breast cancer model shows reduced toxicity and a substantial reduction in tumor weight compared to the free DOX group. These findings confirm the approach's effectiveness for breast cancer treatment and pave the way for innovative solutions in nanomedicine, providing a practical microfluidic mixing system for the design and large-scale production of nanomedicines.