Controlled Drug Release Research Articles

Recent Advances and Future Prospects in Polymer-Mediated Drug Delivery Systems: A Comprehensive Review.

Polymer-based drug carriers have revolutionized the pharmaceutical landscape, providing innovative approaches for efficient drug delivery. These advanced systems have significantly mitigated traditional challenges, offering new avenues for targeted and controlled drug release. This paper aims to explore polymers, focusing on their classification, properties, drug release mechanisms, and pharmaceutical applications while emphasizing recent advancements and future prospects in the field. Polymers can be classified based on their origin, biodegradability, and physical properties. Their unique characteristics, such as biocompatibility, flexibility, and ability to modify surface properties, make them ideal for drug delivery applications. The review delves into various drug release mechanisms employed by polymer-based systems, including diffusion, degradation, swelling, and stimuli-responsive release. These mechanisms ensure a controlled and sustained release of therapeutic agents, enhancing efficacy and reducing side effects. The pharmaceutical applications of polymer-based drug carriers are vast, encompassing targeted delivery to specific tissues or cells, sustained-release formulations, and the delivery of complex molecules like proteins and nucleic acids. Despite their advantages, polymer-based drug delivery systems face limitations, including potential toxicity, stability issues, and manufacturing challenges. Addressing these limitations through continued research and development is crucial for advancing the field. Recent advancements, such as smart polymers and nanotechnology integration, hold promise for overcoming these challenges and improving drug delivery efficiency. In conclusion, polymer-mediated drug delivery systems represent a significant leap forward in pharmaceutical technology. This review highlights the importance of polymers in modern medicine, their potential to revolutionize drug delivery, and the ongoing efforts to optimize their use in clinical applications.

Tailoring pH-sensitive carboxymethyl tamarind kernel gum-based hydrogel for an efficient delivery of hydrophobic drug indomethacin

Polyacrylamide hydrogels have gained attention in the drug delivery field for their pH-dependent nature. Nevertheless, their limited degradability and lower entrapment efficiency for hydrophobic drugs hinder their utility in controlled drug release. This research aims to design a degradable pH-sensitive hydrogel for delivering the hydrophobic drug indomethacin to the colon. This work developed and optimized the hydrogels based on β-cyclodextrin, carboxymethyl tamarind kernel gum, and polyacrylamide with varying amounts of polyethylene glycol diacrylate. The optimized hydrogel exhibits 76.52 % gel fraction, 89.21 % porosity, 1000.27 % swelling, and 90.0 % equilibrium water content. The hydrogel was characterized using Attenuated Total Reflection-Fourier Transform Infrared spectroscopy, confirming the successful crosslinking of the synthesized hydrogel. Powder X-ray Diffraction revealed their amorphous nature while Scanning Electron Microscopy showed a porous surface morphology of the hydrogel. Moreover, rheology confirmed the hydrogel's elastic nature. Notably, the hydrogel demonstrated a drug release of 60.26 % at pH 7.4. Kinetic modelling of indomethacin release data indicated a Fickian diffusion release mechanism. Cytotoxicity tests on HCT-116 cells showed 79 % viability, and the hydrogel fully degraded within 10 days. These results confirmed the potential of synthesized β-CD/PAM/CMTKG hydrogel for controlled indomethacin delivery to the colon.

Personalization of Intravaginal rings by droplet deposition modeling based 3D printing technology

Intravaginal rings (IVRs) are long-acting drug device systems designed for controlled drug release in the vagina. Commercially available IVRs employ a one-size-fits-all development approach, where all patients receive the same drug in similar doses and frequencies, allowing no space for dosage individualization for specific patients’ needs. To allow flexibility for dosage individualization, this study explores the impact of infill-density on critical characteristics of personalized IVRs, manufactured using droplet deposition modeling three-dimensional (3D) printing technology. The model drug was dispersed on the surface of thermoplastic polyurethane pellets using an oil coating method. IVR infill-density ranged from 60 to 100 %. The compatibility of the drug and matrix was assessed using thermal and spectroscopic analyses. The IVRs were evaluated for weight, porosity, surface morphology, mechanical properties, and in vitro drug release. The results demonstrated high dimensional accuracy and uniformity of 3D-printed IVRs, indicating the robustness of the printing process. Increasing infill-density resulted in greater weight, storage modulus, Young’s modulus, Shore hardness, and compression strength, while reducing the porosity of IVRs. All IVRs showed a controlled drug release pattern when tested under accelerated conditions of temperature for 25 days. Notably, greater infill-densities were associated with a decrease in the percentage of drug released. Overall, the study demonstrated that infill-density was an important parameter for personalizing the critical characteristics of the 3D-printed IVRs to fit individual patient needs.

Gelatin-coated glutathione depletion and oxygen generators in potentiated chemotherapy for pancreatic cancer

Chemotherapy is generally acknowledged as an effective method for pancreatic cancer (PC). However, its treatment efficacy is often compromised due to inefficient drug delivery and drug resistance propensity of tumor tissues. The purpose of this study is to design and develop a novel drug delivery system (Manganese-doped mesoporous silica nanoparticles, Mn-MSN) in which paclitaxel (PTX), a conventional chemotherapeutic agent used to effectively treat pancreatic cancer clinically. Through cross-linking with glutaraldehyde, gelatin (Ge) was encapsulated on the carrier surface, endowing the nanoparticles (Ge-Mn-MSN@PTX) with excellent biocompatibility, low hemolytic activity, and enzyme-responsive degradation. Mn was added for the following purposes: (1) catalyzing hydrogen peroxide (H2O2) to generate oxygen (O2), thereby alleviating tumor hypoxia and drug resistance; (2) depleting glutathione (GSH), inducing intracellular lipid peroxidation and ferroptosis; (3) enabling real-time monitoring of the therapeutic efficacy of the nanoparticles via magnetic resonance imaging (MRI). The experimental results demonstrated that Ge-Mn-MSN@PTX has satisfactory biosafety, antitumor activity, controlled drug release as well as imaging tracking capabilities. In the SW1990 nude mice model, the Ge-Mn-MSN@PTX effectively inhibited tumor growth by suppressing the expression of the resistance protein P-glycoprotein (P-gp) and inducing ferroptosis. In conclusion, the designed gelatin-coated Mn-MSN shows potential for application in future pancreatic cancer therapy.

Core-Shell Microspheres with Encapsulated Gold Nanoparticle Carriers for Controlled Release of Anti-Cancer Drugs.

Cancer is one of the major threats to human health and lives. However, effective cancer treatments remain a great challenge in clinical medicine. As a common approach for cancer treatment, chemotherapy has saved the life of millions of people; however, patients who have gone through chemotherapy often suffer from severe side effects owing to the inherent cytotoxicity of anti-cancer drugs. Stabilizing the blood concentration of an anti-cancer drug will reduce the occurrence or severity of side effects, and relies on using an appropriate drug delivery system (DDS) for achieving sustained or even on-demand drug delivery. However, this is still an unmet clinical challenge since the mainstay of anti-cancer drugs is small molecules, which tend to be diffused rapidly in the body, and conventional DDSs exhibit the burst release phenomenon. Here, we establish a class of DDSs based on biodegradable core-shell microspheres with encapsulated doxorubicin hydrochloride-loaded gold nanoparticles (DOX@Au@MSs), with the core-shell microspheres being made of poly(lactic-co-glycolic acid) in the current study. By harnessing the physical barrier of the biodegradable shell of core-shell microspheres, DOX@Au@MSs can provide a sustained release of the anti-cancer drug in the test duration (which is 21 days in the current study). Thanks to the photothermal properties of the encapsulated gold nanoparticle carriers, the core-shell biodegradable microspheres can be ruptured through remotely controlled near-infrared (NIR) light, thereby achieving an NIR-controlled triggered release of the anti-cancer drug. Furthermore, the route of the DOX-Au@MS-enabled controlled release of the anti-cancer drug can provide durable cancer cell ablation for the long period of 72 h.

A pH-responsive novel delivery system utilizing carbon quantum dots loaded with PT2385 for targeted inhibition of HIF-2α in the treatment of osteoarthritis

BackgroundOsteoarthritis (OA) is a progressive joint disorder marked by the degradation of cartilage. Elevated concentrations of hypoxia-inducible factor-2α (HIF-2α) are intricately linked to the pathological development of OA. PT2385 has demonstrated effective inhibition of HIF-2α, thereby potentially impeding the initial advancement of OA. Nevertheless, challenges persist, including limited penetration into the deeper layers of cartilage, issues related to charge rejection, and a heightened rate of clearance from the joint. These constraints necessitate further consideration and exploration. MethodsIt has been demonstrated that PT2385 exhibits efficient inhibition of HIF-2α expression, thereby contributing to the delay in the progression of osteoarthritis. The pH-responsive attributes of carbon quantum dots, specifically those employing m-phenylenediamine (m-CQDs) coated with bovine serum albumin (BSA), have been systematically evaluated. In both in vitro settings involving cartilage explants and in vivo experiments, the efficacy of BSA-m-CQDs-PT2385 (BCP) has been confirmed in facilitating the transport of PT2385 to the middle and deep layers of cartilage. Furthermore, the BCP system demonstrates controlled drug release contingent upon alterations in environmental pH. ResultsWhile the use of PT2385 alone provides protective effects on chondrocytes within an inflamed environment, there exists an opportunity for further enhancement in its efficacy when administered via intra-articular injection. The BCP formulation, characterized by appropriate particle size and charge, facilitates seamless penetration into cartilage tissue. Additionally, BCP demonstrates the capability to release drugs in response to changes in environmental pH. In vitro experiments reveal that BCP effectively inhibits Hif-2α expression and catabolic factors in chondrocytes. Notably, cartilage explants and in vivo experiments indicate that BCP surpasses PT2385 alone in inhibiting the expression of HIF-2α and matrix metalloproteinase 13, particularly in the middle and deep layers. ConclusionsThe BCP drug delivery system exhibits selective release of PT2385 in response to pH changes occurring during the progression of osteoarthritis (OA), thereby inhibiting HIF-2α expression deep within the cartilage. The use of BCP significantly augments the capacity of PT2385 to retard both cartilage degeneration and the progression of osteoarthritis. Consequently, BCP as an innovative approach utilizing m-CQDs to deliver PT2385 into articular cartilage, shows potential for treating osteoarthritis.This strategy opens new avenues for osteoarthritis treatment.

Nanomedicine Advancements in Cancer Therapy: A Scientific Review

Cancer nanomedicines, characterized by submicrometer-sized formulations, aim to optimize the biodistribution of anticancer drugs by minimizing off-target effects, reducing toxicity, enhancing target site accumulation, and improving overall efficacy. Numerous nanomedicines have been developed to improve the effectiveness and safety of traditional anticancer treatments. These include formulations with carbon nanotubes, nanodiamonds, enzyme-responsive nanoparticles for controlled drug release, dendrimers as nanoparticle drug carriers, quantum dot nanocarrier systems for precise drug delivery, solid lipid nanoparticles, and polymeric nanoparticles designed for targeted drug delivery. Additionally, nanotechnology has been explored in cancer treatment through gene therapy. Despite these advances, the complex nature of carrier materials and functional integration presents challenges in preparing these candidates for clinical translation. Nanotechnology, with its unique features at the nanoscale, offers novel possibilities for developing cancer therapies while increasing efficacy and safety. Although only a few nanotherapeutics have obtained clinical approval, exciting uses for nanotechnology are on the horizon. Nanoparticles possess unique transport, biological, optical, magnetic, electrical, and thermal capabilities due to their small size within the light wavelength spectrum. This results in high surface area-to-volume ratios, allowing for the incorporation of various supporting components in addition to active medicinal substances. These properties aid in solubilization, degradation protection, delayed release, immune response evasion, tissue penetration, imaging, targeted distribution, and triggered activation. In summary, the future of nanomedicine holds promise for introducing innovative platforms in cancer treatment. The research presented underscores the potential for nanoparticles to revolutionize anticancer therapies, enhancing the overall therapeutic approach.

PH‐responsive bionanocomposite pectin grafted with dimethylaminoethyl methacrylate and acrylic acid copolymer along with silver nanoparticles for breast cancer drug delivery

AbstractIn this study, we developed a pH‐responsive hydrogel membrane composed of pectin, dimethylaminoethyl methacrylate (DMAEMA), and acrylic acid (AA) through a free radical‐triggered graft copolymerization method. Freshly formed silver nanoparticles (AgNPs) produced from the reduction reaction were embedded in the produced hydrogel. Pectin‐grafted dimethylaminoethyl methacrylate and acrylic acid copolymer [poly (DMAEMA‐co‐AA)‐g‐pectin] and its bionanocomposite with AgNPs were confirmed by Fourier‐transform infrared spectroscopy (FT‐IR), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). The swelling behavior of poly (DMAEMA‐co‐AA)‐g‐pectin in solutions with diverse pH values was assessed. For use as a controlled drug delivery agent, the hydrogel was loaded with 5‐fluorouracil (5‐FU). The incorporation of AgNPs had a great impact on the entrapment efficiency of 5‐FU. At pH 7.4, nearly 48% of the 5‐FU was released in vitro from the polymeric nanocomposite within 24 h. Moreover, poly (DMAEMA‐co‐AA)‐g‐pectin and poly (DMAEMA‐co‐AA)‐g‐pectin/AgNPs presented high cytocompatibility toward normal skin fibroblast cells (BJ1), and the drug delivery system strongly inhibited human Caucasian breast adenocarcinoma cells (MCF‐7). These results demonstrated that these poly (DMAEMA‐co‐AA)‐g‐pectin/AgNPs are an excellent candidate for use in anticancer drug delivery systems.Highlights Free radical polymerization of nanocomposites incorporated with nanoparticles. Nanoparticles improve the bionanocomposites' drug loading. The developed bionanocomposites exhibit control drug release. The novel bionanocomposites acts as an excellent anticancer drug carrier.

Dipyridamole-grafted copolymer electrospun nanofiber membranes for suppression of peritendinous adhesions

Post-traumatic tendon adhesions significantly affect patient prognosis and quality of life, primarily stemming from the absence of effective preventive and curative measures in clinical practice. Current treatment modalities, including surgical excision and non-steroidal anti-inflammatory drugs, frequently exhibit limited efficacy or result in severe side effects. Consequently, the use of anti-adhesive barriers for drug delivery and implantation at the injury site to address peritendinous adhesion (PA) has attracted considerable attention. Electrospun nanofiber membranes (ENMs) have been extensively employed as drug-delivery platforms. In this study, we fabricated a polylactic acid (PLA)–dipyridamole (DP)-graft copolymer ENM called PLC-DP. This membrane exhibits enzyme-sensitive features, allowing more controlled and sustained drug release compared with conventional drug-loaded ENMs. In experiments, PLC-DP implantation reduced tissue adhesion by 47 % relative to the control group while not adversely affecting tendon healing. Mechanistically, PLC-DP effectively activates the FXYD domain containing ion-transport regulator 2 (FXYD2) protein, thereby downregulating the fibroblast-transforming growth factor beta (TGF-β)/Smad3 signaling pathway. PLC-DP leverages the anti-adhesive properties of DP and the enzyme-sensitive characteristics of graft copolymers, providing a promising approach for the future clinical treatment and prevention of PA. Statement of significancePeritendinous adhesions (PA) are a common and disabling condition that seriously affects the prognosis and quality of life of post-trauma patients. Current treatments often have limited efficacy or severe side effects, leaving a serious gap in clinical practice. We developed a significant biomaterial, poly(lactic acid)-dipyridamole graft copolymer electrospun nanofibrous membrane (PLC-DP), specifically for PA inhibition. In addition, this study uniquely combines dipyridamole, an anti-adhesive agent, and enzyme-sensitive copolymers in electrospun nanofibrous membrane. Unlike conventional drug-loaded electrospun nanofibrous membranes, PLC-DPs have enzyme-sensitive drug properties that allow for sustained drug release on demand. Our experiments showed that implantation of PLC-DP was effective in reducing tissue adhesions by 47 % without affecting tendon healing. We elucidated the mechanism behind this phenomenon, suggesting that PCD activates FXYD2 to inhibit TGF-β-induced expression of Col III, which is a key factor in PA development.

Controlled release of doxorubicin from Poly-(D,L-lactide-co-glycolide) (PLGA) nanoparticles prepared by coaxial electrospraying

Enhancing the efficacy and reducing the toxicity of chemotherapeutic agents like doxorubicin (DOX) is crucial in cancer treatment. Core-shell nanoparticles (NPs) fabricated by coaxial electrospraying offer controlled release of anticancer agents with the polymer shell protecting drug molecules from rapid degradation, prolonging therapeutic effect. This study developed DOX-loaded poly(lactic-co-glycolic acid) (PLGA) NPs. NPs were fabricated with matrix or core–shell structure via single needle or coaxial electrospraying, respectively. Core-shell NPs exhibited high encapsulation efficiency (>80 %) with controlled DOX distribution. Compared to matrix NPs, core–shell NPs demonstrated slower sustained release (69 % in 144 h) after reduced initial burst (22 % in 8 h). Release kinetics followed a diffusion mechanism when compared to free drug and matrix DOX-loaded NPs. In vitro assays showed core–shell NPs’ enhanced cytotoxicity against breast cancer cells MCF-7, with higher uptake observed by fluorescence microscopy and flow cytometry. The IC50 for core-shell NPs displayed a significant drop (0.115 μg/mL) compared to matrix NPs (0.235 μg/mL) and free DOX (1.482 μg/mL) after 72 h. Coaxial electrospraying enables the production of therapeutically advantageous core–shell NPs, offering controlled drug release with high encapsulation efficiency, potentially improving clinical anticancer chemotherapy.

Synergistic effect of curcumin and tamoxifen loaded in pH-responsive gemini surfactant nanoparticles on breast cancer cells

BackgroundDrug combination therapy is preferred over monotherapy in clinical research to improve therapeutic effects. Developing a new nanodelivery system for cancer drugs can reduce side effects and provide several advantages, including matched pharmacokinetics and potential synergistic activity. This study aimed to examine and determine the efficiency of the gemini surfactants (GSs) as a pH-sensitive polymeric carrier and cell-penetrating agent in cancer cells to achieve dual drug delivery and synergistic effects of curcumin (Cur) combined with tamoxifen citrate (TMX) in the treatment of MCF-7 and MDA-MB-231 human BC cell lines.MethodsThe synthesized NPs were self-assembled using a modified nanoprecipitation method. The functional groups and crystalline form of the nanoformulation were examined by Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and dynamic light scattering (DLS) used to assess zeta potential and particle size, and the morphological analysis determined by transmission electron microscopy (TEM). The anticancer effect was evaluated through an in vitro cytotoxicity MTT assay, flow cytometry analysis, and apoptosis analysis performed for mechanism investigation.ResultsThe tailored NPs were developed with a size of 252.3 ± 24.6 nm and zeta potential of 18.2 ± 4.4 mV capable of crossing the membrane of cancer cells. The drug loading and release efficacy assessment showed that the loading of TMX and Cur were 93.84% ± 1.95% and 90.18% ± 0.56%, respectively. In addition, the drug release was more controlled and slower than the free state. Polymeric nanocarriers improved controlled drug release 72.19 ± 2.72% of Tmx and 55.50 ± 2.86% of Cur were released from the Tmx-Cur-Gs NPs after 72 h at pH = 5.5. This confirms the positive effect of polymeric nanocarriers on the controlled drug release mechanism. moreover, the toxicity test showed that combination-drug delivery was much more greater than single-drug delivery in MCF-7 and MDA-MB-231 cell lines. Cellular imaging showed excellent internalization of TMX-Cur-GS NPs in both MCF-7 and MDA-MB-231 cells and synergistic anticancer effects, with combination indices of 0.561 and 0.353, respectively.ConclusionThe combined drug delivery system had a greater toxic effect on cell lines than single-drug delivery. The synergistic effect of TMX and Cur with decreasing inhibitory concentrations could be a more promising system for BC-targeted therapy using GS NPs.

Recent developments in intranasal drug delivery of nanomedicines for the treatment of neuropsychiatric disorders.

Neuropsychiatric disorders are multifaceted syndromes with confounding neurological explanations. It includes anxiety, depression, autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, Tourette's syndrome, delirium, dementia, vascular cognitive impairment, and apathy etc. Globally, these disorders occupy 15% of all diseases. As per the WHO, India has one of the largest populations of people with mental illnesses worldwide. The blood-brain barrier (BBB) makes it extremely difficult to distribute medicine to target cells in the brain tissues. However, it is possible through novel advancements in nanotechnology, molecular biology, and neurosciences. One such cutting-edge delivery method, nose-to-brain (N2B) drug delivery using nanoformulation (NF), overcomes traditional drug formulation and delivery limitations. Later offers more controlled drug release, better bioavailability, improved patient acceptance, reduced biological interference, and circumvention of BBB. When medicines are delivered via the intranasal (IN) route, they enter the nasal cavity and go to the brain via connections between the olfactory and trigeminal nerves and the nasal mucosa in N2B. Delivering phytochemical, bioactive and synthetic NF is being investigated with the N2B delivery strategy. The mucociliary clearance, enzyme degradation, and drug translocations by efflux mechanisms are significant issues associated with N2B delivery. This review article discusses the types of neuropsychiatric disorders and their treatment with plant-derived as well as synthetic drug-loaded NFs administered via the IN-delivery system. In conclusion, this review provided a comprehensive and critical overview of the IN applicability of plant-derived NFs for psychiatric disorders.

Controlled released dynamics of methotrexate from chitosan-based capsules: A detailed energy landscape analysis

Polymeric membranes are extensively used to construct vehicles for various drug delivery applications. In this study, we investigated the potential of chitosan-based membranes as a carrier for the controlled release of methotrexate (MTX), a widely used drug in cancer treatment. The chitosan (CS) chains were cross-linked with sodium tripolyphosphate (STPP) to form a rigid matrix capable of encapsulating MTX. Molecular dynamics simulations were employed to assess the performance of the CS-based membranes in releasing MTX upon exposure to water. We have calculated the potential of mean force to understand the energy landscape in the aqueous medium or ethanol-water solution. We have observed that the free energy in the ethanol-water solution reduced to ∼52.4 kcal/mol as compared to an aqueous solution. In addition, we have shown the effect of the concentration of STPP on the binding of CS with MTX. Understanding how STPP concentration affects MTX release is crucial for designing drug delivery systems. By adjusting the concentration of STPP, one can fine-tune the release profile of the drug. We have also shown the comparative study of energy requirement to release a drug molecule from the CS matrix with and without STPP molecules. The pair correlation displayed that the water molecules have a stronger interaction with the STPP molecules compared to CS chains and MTX molecules. Our findings indicate that the CS nanoparticles exhibit promising characteristics for controlled drug release, making them a potential candidate for improving the efficacy and safety of MTX therapy in cancer treatment.

A Complete Appraisal of Polymeric Micelle-Based Nanocarrier for Targeting Breast Cancer: Recent Strategies and Advancements

Aim/Objective: Polymeric micelle-based drug delivery systems have emerged as a beacon of hope in the challenging landscape of breast cancer therapy. This review aimed to explore the recent advancements and promising developments in the field, offering an in-depth analysis of their potential and challenges. The significance of this study lies in providing a comprehensive examination of the current advances in polymeric micelles technology, which have the potential to improve the efficiency and specificity of breast cancer therapy while minimizing adverse events. Methods: Polymeric micelles offer a revolutionary therapy by encapsulating therapeutic agents, allowing for controlled drug release and the precise targeting of malignant cells, while lowering systemic toxicity. Recent advances have focused on enhancing targeting strategies, including active and passive targeting, to increase the specificity of polymeric micelle-based therapies. A systematic review of literature was carried out using databases, like PubMed, Scopus, and Web of Science, which included papers published between 2010 and 2023. The selection criteria of the literature focused on the drug-loading capabilities and targeting strategies of the polymeric micelles, which could be advantageous for breast cancer treatment. Results: Clinical drug approaches leverage the versatility of micelles to co-deliver multiple agents, addressing the multifaceted nature of breast tumors and combating drug resistance. Additionally, polymeric micelles are finding applications in breast cancer diagnostics and imaging, enabling early detection and precise monitoring. The journey of polymeric micelle-based breast cancer therapy extends to formulation and engineering, preclinical and clinical studies, and confronts regulatory and commercialization challenges. However, the horizon is illuminated by emerging technologies, like personalized medicine, biomarker-driven targeting, and integration with novel therapies, promising a future where breast cancer treatment is tailored to individual patients and marked by improved efficacy and reduced side effects. Conclusion: In conclusion, this review underscores the transformative potential of polymeric micelle- based delivery systems in breast cancer therapy.

An advanced ultrasound-activated drug delivery system with piezocatalytic MoS2 nanoflowers for treating patent ductus arteriosus

Patent ductus arteriosus (PDA) is a prevalent cardiovascular anomaly that leads to considerable morbidity and mortality in premature infants. Although pharmacological interventions are commonly used for treatment, they often have notable adverse effects. This study introduces an innovative approach: a controlled drug delivery system that utilizes piezocatalyst nanocarriers produced through hydrothermal techniques. The synthesized nanoparticles undergo thorough characterization to assess their structural and morphological properties. Through ultrasound treatment, precise drug loading and efficient release of indomethacin (IDM) from chitosan (CS) stabilized molybdenum disulfide nanoflowers (MoS2-CS-IDM) are achieved. By harnessing ultrasound-induced reactive oxygen species, this method enables targeted drug delivery. Importantly, the nanoparticles demonstrate an approximately 60 % decrease in PGE2 concentrations, indicating their potential as anti-inflammatory agents. The favorable interaction of the nanoparticles with rat aortic smooth muscle cells and the successful closure of the ductus arteriosus in fetal Wistar rats validate their therapeutic effectiveness in vivo. In conclusion, the piezocatalyst-based drug delivery system presented in this study holds promise for versatile, biocompatible, and controlled drug release, with significant implications for therapeutic applications in PDA and potentially beyond.

Antimicrobial Peptide Hydrogel with pH-Responsive and Controllable Drug Release Properties for the Efficient Treatment of Helicobacter pylori Infection.

Helicobacter pylori is the primary cause of gastric adenocarcinoma, which afflicts more than half of the world's population and seriously affects human health. However, achieving efficient treatment of H. pylori infection by effective drug delivery and bioavailability after oral administration remains a challenge due to the harsh microenvironment, short drug retention time, and physiological barriers in the stomach. Moreover, H. pylori has shown resistance to many clinical antibiotics. Antimicrobial peptides (AMPs) exhibit substantial therapeutic efficacy against H. pylori, while they are not likely to induce drug resistance, suggesting their potential utility for the treatment of diseases related to H. pylori. In this paper, we report the design and synthesis of an AMP (GE33) hydrogel with pH-responsive and controlled peptide release properties, in which the minimal inhibitory concentration of the AMP against H. pylori is as low as 1 μg/mL. GE33 self-assembles into a stable peptide hydrogel under neutral pH conditions but decomposes into monomers or oligomers under acidic conditions. Upon oral administration of the hydrogel, the acidic gastric environment would facilitate rapid release of active AMP molecules from the hydrogel and immediate targeting of H. pylori in the stomach wall. Additionally, the remaining peptide is protected in the hydrogel, extending its retention time in the stomach, so that persistent drug release is achieved. The controlled and sustained release manner of the active molecule GE33, which enhances drug bioavailability, along with its excellent bactericidal efficacy opens a great potential for treating H. pylori infection.

Dual folate/biotin-decorated liposomes mediated delivery of methylnaphthazarin for anti-cancer activity

Chemotherapy is an effective strategy for mitigating the global challenge of cancer treatment, which often encounters drug resistance and negative side effects. Methylnaphthazarin (MNZ), a natural compound with promising anti-cancer properties, has been underexplored due to its poor aqueous solubility and low selectivity. This study introduces a novel approach to overcome these limitations by developing MNZ-encapsulating liposomes decorated with folate and biotin (F/B-LP-MNZ). This dual-targeting strategy aims to enhance the anti-cancer efficacy and specificity of MNZ delivery. Our innovative F/B-LP-MNZ formulation demonstrated excellent physicochemical properties, stability, and controlled drug release profiles. In vitro studies revealed that MNZ-loaded liposomes attenuate the toxicity associated with free MNZ while F/B-LP-MNZ significantly increased cytotoxicity against HeLa cells, which express high levels of folate and biotin receptors, compared to non-targeted liposomes. Enhanced cellular uptake and improved dynamic flow attachment further confirmed the superior specificity of F/B-LP in targeting cancer cells. Additionally, our results revealed that F/B-LP-MNZ effectively inhibits HeLa cell migration and adhesion through EMT suppression and apoptotic induction, indicating its potential to prevent cancer metastasis. These findings highlight the potential of dual folate and biotin receptors-targeting liposomes as an effective delivery system for MNZ, offering a promising new avenue for targeted cancer therapy.

Preparation, characterization, and binding mechanism of quercetin-loaded composite nanoparticles based on zein-soybean protein isolate

In this study, quercetin (Que) was encapsulated for controlled release during gastrointestinal digestion using zein–soy isolate protein (SPI) composite nanoparticles that were made following an antisolvent precipitation technique. The average particle size of the composite nanoparticles ranged from 182.1 to 230.9 nm, and the polydispersity index (PDI) was small (0.105–0.323). The microstructure revealed that the composite nanoparticles were spherically distributed and that Que. was embedded on the surface of the nanoparticles. Que. has an encapsulation efficiency of up to 93.3 %. Spectrum analysis, molecular docking and zeta potential measurements revealed that the interactions between the composite nanoparticles and Que. occurred mainly through hydrophobic interactions, hydrogen bonding, and electrostatic interactions. Compared with single zein nanoparticles, the composite nanoparticles showed a significant and controlled release of Que. during the whole simulated gastrointestinal digestion process. This study provides a novel method for the development of a controlled-release drug delivery system for controlling the release of Que.

Development of a Controllable Intelligent Drug Delivery System for Efficient Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a complex inflammatory disease of the joints, which is often accompanied by degeneration of articular cartilage and bone erosion, seriously affecting the quality of life and psychological state of patients. RA is difficult to be cured completely, and currently the main purpose of relief is through the use of anti-inflammatory and antirheumatic drugs, hormones, and biological agents. Tofacitib is a new type of small molecule inhibitor, which has a good effect in the treatment of RA. The current direct drug delivery method has serious side effects caused by the systemic distribution of the drug, so there is a need to develop an intelligent drug delivery system to realize precise treatment. In this work, tofacitib, gallic acid, targeted molecule folic acid, and Fe(III) were selected to assemble a novel type of artificial controllable nanodrug GF-TF. The self-photoacoustic/magnetic resonance imaging (self-PA/MRI) monitored the enrichment of GF-TF in the lesion in real-time, and artificially regulated the addition of deferoxamine (DFO) at the optimal enrichment. DFO strongly chelates Fe(III) in GF-TF and causes its structure to disintegrate gradually, and the self-PA/MRI signal of GF-TF became weaker while tofacitib began to be released, thus realizing the precise and artificially controlled release of the drug under the guidance of imaging. This nanodrug not only achieves efficient aggregation of drugs in inflamed joints, but also achieves real-time monitoring and precise control of drug release through self-PA/MRI, providing a new strategy for the precise treatment of RA.

“Bamboo-like” strong and tough sodium alginate/polyacrylate hydrogel fiber with directional controlled release for wound healing promotion

Skin, as the biggest organ and outermost surface of the human body, is prone to injury due to various challenges, especially the expanding potential of accidents, which bring a huge social and economic burden. Hydrogels are emerging as the most promising candidate for wound dressings, which not only fulfill the varied requirements of dressings but also serve as drug carriers. But limited breathability, rapid drug release, and inadequate mechanical properties remains a significant challenge. Herein, we report a strong and tough sodium alginate/polyacrylate hydrogel fibers-based dressing with directional controlled drug release for wound healing promotion. Mimicking the bamboo structure, the drug solution is encapsulated within the fiber, and the rate of drug release can be modulated by controlling the wall thickness of the fiber. A cross-network structure in the hydrogel fiber through hydrogen bond and calcium ion crosslinking resulted in a 38 % increase in tensile strength. By precisely controlling the feeding process during weaving, drug-loaded fibers can be prepared at specific locations to facilitate targeted delivery to skin wound sites. Drug-loaded fabric has the breathability and biocompatibility required for dressings to promote wound healing. The findings highlight the potential of alginate/polyacrylate hydrogel fabrics for effective wound treatment.