Development Of Drug Delivery Systems Research Articles

Transformative Impact of Nanocarrier‐Mediated Drug Delivery: Overcoming Biological Barriers and Expanding Therapeutic Horizons

Advancing therapeutic progress is centered on developing drug delivery systems (DDS) that control therapeutic molecule release, ensuring precise targeting and optimal concentrations. Targeted DDS enhances treatment efficacy and minimizes off‐target effects, but struggles with drug degradation. Over the last three decades, nanopharmaceuticals have evolved from laboratory concepts into clinical products, highlighting the profound impact of nanotechnology in medicine. Despite advancements, the effective delivery of therapeutics remains challenging because of biological barriers. Nanocarriers offer a solution with a small size, high surface‐to‐volume ratios, and customizable properties. These systems address physiological and biological challenges, such as shear stress, protein adsorption, and quick clearance. They allow targeted delivery to specific tissues, improve treatment outcomes, and reduce adverse effects. Nanocarriers exhibit controlled release, decreased degradation, and enhanced efficacy. Their size facilitates cell membrane penetration and intracellular delivery. Surface modifications increase affinity for specific cell types, allowing precise treatment delivery. This study also elucidates the potential integration of artificial intelligence with nanoscience to innovate future nanocarrier systems.

Extracellular vesicles-hitchhiking boosts the deep penetration of drugs to amplify anti-tumor efficacy

Developing drug delivery systems capable of achieving deep tumor penetration is a challenging task, yet there is a significant demand for such systems in cancer treatment. Hitchhiking on tumor-derived extracellular vesicles (EVs) represents a promising strategy for enhancing drug penetration into tumors. However, the limited drug assembly on EVs restricts its further application. Here, we present a novel approach to efficiently attach antitumor drugs to EVs using an engineered cell membrane-based vector. This vector includes the AS1411 aptamer for tumor-specific targeting, the vesicular stomatitis virus glycoprotein (VSV-G) for tumor cell membrane fusion, and a photosensitizer as the therapeutic agent while ensuring optimal drug encapsulation and stability. Upon injection, photosensitizers are firstly transferred to the tumor cell membrane and subsequently piggybacked onto EVs with the inherent secretion process. By hitchhiking with EVs, photosensitizers can be transferred layer by layer deep into the solid tumors. The results suggest that this EVs-hitchhiking strategy enables photosensitizers to penetrate deeply into tumor tissue, thereby enhancing the efficacy of phototherapy. This study offers broad application prospects for delivering drugs deeply into tumor tissues.

Synergistic effect of waste-derived β-tricalcium phosphate microbeads loaded in hydroxyapatite-keratin-polyvinyl alcohol composite matrix in drug release for osteosarcoma treatment

BackgroundSustained drug delivery system (DDS) for clinically relevant osteosarcoma medications is a promising strategy for treatment. β-tricalcium phosphate (β-TCP) microbeads loaded with doxorubicin hydrochloride (DOX) and cis-diamminedichloroplatin (CDDP) anticancer drugs in a matrix of hydroxyapatite-keratin-polyvinyl alcohol composite matrix scaffolds (HAp-K-PVA) was developed as promising DDS. HAp, β-TCP, and K utilized for the development of DDS were resourced from avian eggshells and human hairs, respectively, and duly characterized before application.MethodsThe β-TCP/alginate microbeads were fabricated using droplet extrusion and ionotropic gelation, and integrated into secondary drug carrier HAp-K-PVA composite matrix, via freeze gelation. The physicochemical and thermal characterization of developed microbeads and matrix scaffolds was performed.ResultsWhen DOX and CDDP were co-loaded in DDS, a synergistic impact was observed after 30 days of continuous release, in contrast to the immediate outburst as seen with individual DOX and CDDP releases. Besides, the drug release from the microbeads only, the release with the HAp-K-PVA composite matrix scaffolds was observed slower. The controlled release, antibacterial effectiveness against the test pathogens and cell viability with osteoblast-like osteosarcoma (UTOS) cells indicated the therapeutic potential for the treatment of osteosarcoma in situ. The cell viability was observed for 24 h, which showed nearly 90% after 24 h for HAp-K-PVA composite matrix scaffolds, decreased for all the scaffold groups after 72 h, indicating the enhancement due to combined synergistic effect of the co-loaded drugs.ConclusionThis study established a promising foundation for novel and sustainable biomaterials for osteosarcoma treatment. Further advancement holds the potential to enhance patient clinical outcomes and foster advancements in the field of regenerative medicine.

Plant-derived extracellular vesicles: a synergetic combination of a drug delivery system and a source of natural bioactive compounds.

Exosomes are extracellular nanovesicles secreted by all cell types and have been studied to understand and treat many human diseases. Exosomes are involved in numerous physiological and pathological processes, intercellular communication, and the transfer of substances. Over the years, several studies have explored mammalian-derived exosomes for therapeutic and diagnostic uses. Only recently have plant-derived extracellular vesicles (EVs) attracted attention for their ability to overcome many defects associated with using mammalian-derived extracellular vesicles, such as safety and scale-up issues. The ease of large-scale production, low toxicity, low immunogenicity, efficient cellular uptake, high biocompatibility, and high stability of these nanovesicles make them attractive for drug delivery systems. In addition, their native contents of proteins, miRNAs and secondary metabolites could be exploited for pharmaceutical applications in combination with other drugs. The present review intends to provide adequate tools for studying and developing drug delivery systems based on plant-derived EVs. Therefore, indications concerning extraction methods, characterisation, and drug loading will be offered. Their biological composition and content will also be reported. Finally, the current applications of these systems as nanocarriers for pharmacologically active substances will be shown.

Surgery Combined with Local Implantation of Doxorubicin-Functionalized Hydroxyapatite Halts Tumor Growth and Prevents Bone Destruction in an Aggressive Osteosarcoma.

Osteosarcoma treatment comprises pre-surgical chemotherapy followed by radical surgery and further chemotherapy cycles, but the prognosis has been far from satisfactory. No new drugs or treatment modalities have been developed for clinical use in the last four decades. We describe a nano-hydroxyapatite (HA)-based local drug delivery platform for the delivery of doxorubicin (DOX), a cornerstone drug in osteosarcoma treatment. The efficacy of the developed drug delivery system was evaluated in an orthotopic human osteosarcoma xenograft in the proximal tibia of mice. After tumor development, the tumor was surgically resected and the void filled with the following: (1) No treatment (G1); (2) nHA only (G2); (3) DOX-loaded nHA (G3). In-vivo tumor response was assessed by evaluating the tumor-induced osteolysis at 2 weeks using micro-CT followed by in-vivo PET-CT at 3 weeks and ex-vivo micro-CT and histology. Micro-CT imaging revealed complete destruction of the tibial metaphysis in groups G1 and G2, while the metaphysis was protected from osteolysis in G3. PET-CT imaging using 18F-FDG revealed high metabolic activity in the tumors in G1 and G2, which was significantly reduced in G3. Using histology, we were able to verify that local DOX delivery reduced the bone destruction and the tumor burden compared with G1 and G2. No off-target toxicity in the vital organs could be observed in any of the treatment groups histologically. This study describes a novel local drug adjuvant delivery approach that could potentially improve the prognosis for patients responding poorly to the current osteosarcoma treatment.

AB001. Development of tumour-targeted therapy for the treatment of adult and paediatric high-grade gliomas.

Brain cancer patients, especially those suffering from high-grade gliomas (HGGs) face a bleak future with very dismal long-term disease-free survival outcomes due to the limited treatment options currently available. Therefore, there is an unmet need for new therapeutic intervention that extends patients' progress-free survival and improves their quality of life. A significant hurdle is the inability of current chemotherapy agents to cross the blood-brain barrier (BBB). BBB acts as a protective shield that filters the blood to ensure nothing harmful makes it to the brain. This protection is usually good, but it becomes a problem if you want to deliver therapeutic cancer drugs through it. This barrier blocks 98% of drugs from entering the brain. Even the ones that cross BBB are unevenly distributed in the normal brain and tumour tissue, resulting in mediocre treatment and severe side effects. We are developing drug delivery systems that can cross the BBB and facilitate the specific accumulation of drugs in the tumour tissue. This will significantly improve the efficacy of anticancer drugs in treating various brain cancers and reduce systemic toxicity. Our group has explored and developed BBB crossing and tumour targeting near infra-red dyes, which can be covalently attached to Food and Drug Administration (FDA)-approved chemotherapy agents (drug-dye conjugates), thereby delivering it to the tumour tissue. We synthesized such drug-dye conjugates to target various aberrant pathways in HGG and tested these conjugates against patient-derived HGG cell lines. One such conjugate was tested on a mouse model of glioblastoma, an aggressive form of HGG, and shown to cross the BBB and specifically accumulate in tumour tissue, bringing forth tumour burden reduction. The results obtained from this work serve as proof of principle that enables tumour-specific drug delivery to treat HGG. This work also paves the way for treating other brain cancers and central nervous system (CNS) disorders like Parkinson's and Alzheimer's disease, for which no adequate therapy exists.

Recent Progress in Multifunctional Stimuli-Responsive Combinational Drug Delivery Systems for the Treatment of Biofilm-Forming Bacterial Infections.

Drug-resistant infectious diseases pose a substantial challenge and threat to medical regimens. While adaptive laboratory evolution provides foresight for encountering such situations, it has inherent limitations. Novel drug delivery systems (DDSs) have garnered attention for overcoming these hurdles. Multi-stimuli responsive DDSs are particularly effective due to their reduced background leakage and targeted drug delivery to specific host sites for pathogen elimination. Bacterial infections create an acidic state in the microenvironment (pH: 5.0-5.5), which differs from normal physiological conditions (pH: 7.4). Infected areas are characterized by the overexpression of hyaluronidase, gelatinase, phospholipase, and other virulence factors. Consequently, several effective stimuli-responsive DDSs have been developed to target bacterial pathogens. Additionally, biofilms, structured communities of bacteria encased in a self-produced polymeric matrix, pose a significant challenge by conferring resistance to conventional antimicrobial treatments. Recent advancements in nano-drug delivery systems (nDDSs) show promise in enhancing antimicrobial efficacy by improving drug absorption and targeting within the biofilm matrix. nDDSs can deliver antimicrobials directly to the biofilm, facilitating more effective eradication of these resilient bacterial communities. Herein, this review examines challenges in DDS development, focusing on enhancing antibacterial activity and eradicating biofilms without adverse effects. Furthermore, advances in immune system modulation and photothermal therapy are discussed as future directions for the treatment of bacterial diseases.

Antioxidant, Antitumoral, Antimicrobial, and Prebiotic Activity of Magnetite Nanoparticles Loaded with Bee Pollen/Bee Bread Extracts and 5-Fluorouracil.

The gut microbiota dysbiosis that often occurs in cancer therapy requires more efficient treatment options to be developed. In this concern, the present research approach is to develop drug delivery systems based on magnetite nanoparticles (MNPs) as nanocarriers for bioactive compounds. First, MNPs were synthesized through the spraying-assisted coprecipitation method, followed by loading bee pollen or bee bread extracts and an antitumoral drug (5-fluorouracil/5-FU). The loaded-MNPs were morphologically and structurally characterized through transmission electron microscopy (TEM), selected area electron diffraction (SAED), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Dynamic Light Scattering (DLS), and thermogravimetric analysis. UV-Vis spectroscopy was applied to establish the release profiles and antioxidant activity. Furthermore, the antibacterial and antitumoral activity of loaded-MNPs was assessed. The results demonstrate that MNPs with antioxidant, antibacterial, antiproliferative, and prebiotic properties are obtained. Moreover, the data highlight the improvement of 5-FU antibacterial activity by loading on the MNPs' surface and the synergistic effects between the anticancer drug and phenolic compounds (PCs). In addition, the prolonged release behavior of PCs for many hours (70-75 h) after the release of 5-FU from the developed nanocarriers is an advantage, at least from the point of view of the antioxidant activity of PCs. Considering the enhancement of L. rhamnosus MF9 growth and antitumoral activity, this study developed promising drug delivery alternatives for colorectal cancer therapy.

Surface modification of carbon dots with cyclodextrins as potential biocompatible photoluminescent delivery/bioimaging nanoplatform

BackgroundCyclodextrins are a well-established system which form inclusion complexes with many guest molecules. This property can be easily exploited to develop drug delivery systems. Additionally, carbon dots (CD) are a low-toxic photoluminescent product which have been used as luminescent tags. The combination of cyclodextrins and carbon dots allows obtaining a new nanoplatform, a biocompatible material, with both capabilities, increasing as well the internalization by the cells of the CD, induced by the cyclodextrins. ResultsIn the present work, we have modified the surface of carbon dots obtained from citric acid and glutathione with β and γ cyclodextrins. After a morphological and spectroscopic characterization, we concluded that the luminescence quantum yield and absorption molar coefficient of the derivatized and unmodified carbon dots was the same. These findings, together with the spectroscopic detection of active cyclodextrins, those bond to the CD able to interact with a guest molecule, allowed determination of the ratios: cyclodextrins/CD, active cyclodextrins/CD and an estimation of the CD molecular mass. Furthermore, the biocompatibility of the new materials was evaluated through cytotoxicity and cell-penetrance assays revealing that the materials were non cytotoxic up to 0.1 mg/mL. Moreover, the biocompatible developed nanoplatform penetrates in the cells maintaining the material's intrinsic fluorescence, thus constituting an adequate photoluminescent-tag with high-contrast for in vitro cell imaging. SignificanceThis work provides a new and easy method to combine cyclodextrins and carbon dots into a biocompatible material which can be used as nanoplatform both as drug delivery system and as photoluminescent tag in cell imaging. Likewise, this paper shows how to characterize the number of cyclodextrins and active cyclodextrins per CD, having an average stoichiometric relation of 1:1 for guest molecule – CD. Additionally, the minimum molecular mass of the unmodified CD was indirectly obtained, yielding about 1.6–1.9 kDa.

Irinotecan-loaded magnetite-silica core-shell systems for colorectal cancer treatment

Colorectal cancer represents a worldwide spread type of cancer and it is regarded as one of the leading death causes, along with lung, breast, and prostate cancers. Since conventional surgical resection and chemotherapy proved limited efficiency, the use of alternative drug delivery systems that ensure the controlled release of cytostatic agents possess immense potential for treatment. In this regard, the present study aimed to develop and evaluate the efficiency of a series of irinotecan-loaded magnetite-silica core–shell systems. The magnetite particles were obtained through a solvothermal treatment, while the silica shell was obtained through the Stöber method directly onto the surface of magnetite particles. Subsequently, the core–shell systems were physico-chemically and morpho-structurally evaluated trough X-ray diffraction (XRD) and (high-resolution) transmission electron microscopy ((HR-)TEM) equipped with a High Annular Angular Dark Field Detector (HAADF) for elemental mapping. After the irinotecan loading, the drug delivery systems were evaluated through Fourier-transform infrared spectroscopy (FT-IR), thermogravimetry and differential scanning calorimetry (TG-DSC), and UV–Vis spectrophotometry. Additionally, the Brunauer–Emmett-Teller (BET) method was employed for determining the surface area and pore volume of the systems. The biological functionality of the core-shells was investigated through the MTT assay performed on both normal and cancer cells. The results of the study confirmed the formation of highly crystalline magnetite particles comprising the core and mesoporous silica layers of sizes varying between 2 and 7 nm as the shell. Additionally, the drug loading and release was dependent on the type of the silica synthesis procedure, since the lack of hexadecyltrimethylammonium bromide (CTAB) resulted in higher drug loading but lower cumulative release. Moreover, the nanostructured systems demonstrated a targeted efficiency towards HT-29 colorectal adenocarcinoma cells, as in the case of normal L929 fibroblast cells, the cell viability was higher than for the pristine drug. In this manner, this study provides the means and procedures for developing drug delivery systems with applicability in the treatment of cancer.

Local delivery of methotrexate/glycyrrhizin-loaded hyaluronic acid nanofiber for the management of oral cancer

The challenges in treating oral cancer include the limited effectiveness and systemic side effects of conventional chemotherapy and radiation therapy. Hyaluronic acid (HA) based Glycyrrhizin (GL) and Methotrexate (MT) loaded localized delivery systems, specifically nanofiber (NF) based platforms, were developed to address these challenges. The electrospinning method was used for the successful fabrication of a homogenous NF membrane and characterized for morphology, drug entrapment efficiency, tensile strength, and ex-vivo mucoadhesive study. Also, it was evaluated for in-vitro drug release profile, ex-vivo drug permeability, in-vitro anti-inflammatory, apoptosis assay by MTT and flow, and against specific cell lines in order to determine their potential for therapeutic use. Superior tensile breaking force (50 g), mucoadhesive strength of 153 gm/cm2, drug permeability, and releasing properties of designed NF, making them perfect requirements for oral cavity delivery. The anticancer potential of MT in the MTT assay and flow cytometry analysis was significantly increased in oral epidermal carcinoma cell (KB cell) for drug-loaded NF with 63.97 ± 1.99 % apoptosis, at 24 h. With these incorporated, GL with MT in NF had an anti-inflammatory potential, also demonstrated in-vitro and in-vivo. In the Ehrlich Ascites Carcinoma (EAC) induced mice model, the optimal formulation’s shows better potential for tumor regression when comparing the developed NF formulation to the drugs. Experimental results show that by lowering mucositis-related inflammation and enhancing the effectiveness of oral cancer treatment, a developed nanofiber-based local drug delivery system offers a feasible strategy for managing oral cancer.

Enhancing Infected Diabetic Wound Healing through Multifunctional Nanocomposite-Loaded Microneedle Patch: Inducing Multiple Regenerative Sites.

Infected diabetic wound (DW) presents a prolonged and challenging healing process within the field of regenerative medicine. The effectiveness of conventional drug therapies is hindered by their limited ability to reach deep tissues and promote adequate wound healing rates. Therefore, there is an imperative to develop drug delivery systems that can penetrate deep tissues while exhibiting multifunctional properties to expedite wound healing. In this study, w e devised a soluble microneedle (MN) patch made of γ-PGA, featuring multiple arrays, which w as loaded with core-shell structured nanoparticles (NPs) known as Ag@MSN@CeO2, to enhance the healing of infected DWs. The NP comprises a cerium dioxide (CeO2) core with anti-inflammatory and antioxidant properties, a mesoporous silica NP (MSN) shell with angiogenic characteristics, and an outermost layer doped with Ag to combat bacterial infections. W e demonstrated that the MN platform loaded with Ag@MSN@CeO2 successfully penetrated deep tissues for effective drug delivery. These MN tips induced the formation of multiple regenerative sites at various points, leading to antibacterial, reactive oxygen species-lowering, macrophage ecological niche-regulating, vascular regeneration-promoting, and collagen deposition-promoting effects, thus significantly expediting the healing process of infected DWs. Considering these findings, the multifunctional MN@Ag@MSN@CeO2 patch exhibits substantial potential for clinical applications in the treatment of infected DW.

Baicalin-loaded Polydopamine modified ZIF-8 NPs inhibits myocardial ischemia/reperfusion injury in rats

Baicalin (BAN) has shown promise in alleviating myocardial ischemia/reperfusion (I/R) injury, yet its limited solubility and biocompatibility have hindered its application. Developing drug delivery systems is a promising strategy to enhance the therapeutic potential of BAN in the context of I/R injury. This study aims to prepare a BAN-loaded nanodrug system using polydopamine (PDA)-modified Zeolitic imidazolate framework-8 (ZIF-8) as a carrier, with the goal of improving BAN's mitigating effects on I/R injury. We prepared the BAN nanoparticles (NPs) system, PZB NPs, using ZIF-8 as the carrier. The system was characterized in terms of morphology, particle size, zeta potential, and X-ray diffraction (XRD). We assessed the cytotoxicity of PZB NPs in H9c2 cells, investigated its effects and mechanisms in H/R-induced H9c2 cells, and evaluated its ability to alleviate myocardial I/R injury in rats. PZB NPs exhibited good dispersion, with a BAN loading efficiency of 26.43 ± 1.55%, a hydrated particle size of 102.21 ± 1.19 nm, and a zeta potential of −24.84 ± 0.07 mV. It displayed slow and sustained drug release in an acidic environment (pH 5.5). In vitro studies revealed that PZB NPs was non-cytotoxic and significantly enhanced the recovery of H/R injury H9c2 cell viability. PZB NPs suppressed cell apoptosis, activated the Nrf2/HO-1 pathway, and cleared ROS. In vivo study demonstrated that PZB NPs significantly reduced infarct size, ameliorated fibrosis and improved heart function. The PZB NPs markedly enhances BAN's ability to alleviate I/R injury, both in vitro and in vivo, offering a promising drug delivery system for clinical applications.

Inhalable spray-dried porous microparticles containing dehydroandrographolide succinate phospholipid complex capable of improving and prolonging pulmonary anti-inflammatory efficacy in mice.

Due to the unique physiological barriers within the lungs, there are considerable challenges in developing drug delivery systems enabling prolonged drug exposure to respiratory epithelial cells. Here, we report a PulmoSphere-based dry powder technology that incorporates a drug-phospholipid complex to promote intracellular retention of dehydroandrographolide succinate (DAS) in respiratory epithelial cells following pulmonary delivery. The DAS-phospholipid complex has the ability to self-assemble into nanoparticles. After spray-drying to produce PulmoSphere microparticles loaded with the drug-phospholipid complex, the rehydrated microparticles discharge the phospholipid complex without altering its physicochemical properties. The microparticles containing the DAS-phospholipid complex exhibit remarkable aerodynamic properties with a fine particle fraction of ∼ 60% and a mass median aerodynamic diameter of ∼ 2.3μm. These properties facilitate deposition in the alveolar region. In vitro cell culture and lung tissue explants experiments reveal that the drug-phospholipid complex prolongs intracellular residence time and lung tissue retention due to the slow intracellular disassociation of drug from the complex. Once deposited in the lungs, the DAS-phospholipid complex loaded microparticles increase and extend drug exposure to the lung tissues and the immune cells compared to the free DAS counterpart. The improved drug exposure to airway epithelial cells, but not immune cells, is related to a prolonged duration of pulmonary anti-inflammation at decreased doses in a mouse model of acute lung injury induced by lipopolysaccharide. Overall, the phospholipid complex loaded microparticles present a promising approach for improved treatment of respiratory diseases, e.g. pneumonia and acute respiratory distress syndrome.

Role of mesoporous silica functionalized with boronic acid derivative in targeted delivery of doxorubicin and co-delivery of doxorubicin and resveratrol

Phenylboronic acid derivatives have gained interest due to their ability to reversibly bind to 1,2-diols, such as sialic acid receptors overexpressed by breast cancer cells. In this study, two types of mesoporous silica, MCM-41 and SBA-15, were functionalized with 4-carboxyphenylboronic acid (CPBA) through the amidation reaction, and the resulting materials MCM-CPBA and SBA-CPBA were used as carriers for doxorubicin (Dox) or for co-delivery of doxorubicin and resveratrol. In the case of MCM-CPBA material, all amine groups were involved in the condensation reaction with boronic acid derivative, while in the case of SBA-CPBA, free amine groups remained on the silica surface. Dox release profiles, performed in phosphate buffer solution pH 5.5, showed a faster release kinetics of Dox and a higher cumulative drug release for co-delivery system. Larger pores of SBA-15-type carrier influenced the Dox release profile as the diffusion of drug molecules was favored, a higher cumulative drug release being obtained in the case of SBA-CPBA than for MCM-CPBA. Biological assessment of the developed drug delivery systems demonstrated lower cytotoxicity on BJ fibroblasts than on BT474 breast cancer cells. Evaluation of drug delivery systems by hyperspectral microscopy evidenced a higher internalization rate of Dox when was loaded on functionalized silica carriers compared to the free drug into BT474 cells. The internalization rate of doxorubicin-loaded carrier depended on the type of carrier; a better internalization was observed for cancer cells when were treated with Dox-loaded MCM-CPBA nanoparticles than for Dox-loaded SBA-CPBA that might be attributed to smaller size of MCM-CPBA nanoparticles.

Enhancing the efficacy of letrozole-loaded PEGylated nanoliposomes against breast cancer cells: In vitro study

Considering its overall impact on human health, letrozole (Let) has been described as having significant efficacy that could be improved by developing drug delivery systems. Considering the side effects of Let, this study aims to encapsulate Let in liposomes and PEGylated liposome nanoparticles (Lipo-Let-PEG) and evaluate the cytotoxic effects on the MCF-7 breast cancer cell line. For this purpose, the Lipo-Let-PEG formulation was designed and characterized by SEM, DLS, and FTIR methods, and the drug release from the optimized formulation and the stability of the optimized Lipo-Let-PEG were measured. Furthermore, the cytotoxicity and apoptotic studies were performed using MTT assay and flow cytometric analysis. According to the experimental data, the vesicle size and EE% were 170.05 ± 4.15 nm and 87.21 ± 1.36 %, respectively. The cumulative release from Lipo-Let-PEG at pH 5.4 and 7.4 was also approximately 60 % and 50 %, respectively. MTT results showed that Lip-Let-PEG produced more drug cytotoxicity than Lip-Let against MCF-7 cancer cells and was more compatible with normal cells. The results of apoptosis and cell cycle arrest using flow cytometry show that Lipo-Let-PEG caused the most significant increase in apoptotic rates and cell cycle arrest in cancer cells compared to other treated groups. In conclusion, Lipo-Let-PEG can be used as an anticancer agent by arresting cell cycle progression and inducing apoptosis, which can be applied in future studies to prevent breast cancer development.

Rational Design of Coordination Polymers Composited Hollow Multishelled Structures for Drug Delivery.

Multifunctional drug delivery systems (DDS) are in high demand for effectively targeting specific cells, necessitating excellent biocompatibility, precise release mechanisms, and sustained release capabilities. The hollow multishelled structure (HoMS) presents a promising solution, integrating structural and compositional design for efficient DDS development amidst complex cellular environments. Herein, starting from a Fe-based metal-organic framework (MOF), amorphous coordination polymers (CP) composited HoMS with controlled shell numbers are fabricated by balancing the rate of MOF decomposition and shell formation. Fe-CP HoMS loaded with DOX is utilized for synergistic chemotherapy and chemodynamic therapy, offering excellent responsive drug release capability (excellent pH-triggered drug release 82% within 72h at pH 5.0 solution with doxorubicin (DOX) loading capacity of 284mg g-1). In addition to its potent chemotherapy attributes, Fe-CP-HoMS possesses chemodynamic therapy potential by continuously catalyzing H2O2 to generate ·OH species within cancer cells, thus effectively inhibiting cancer cell proliferation. DOX@3S-Fe-CP-HoMS, at a concentration of 12.5µg mL-1, demonstrates significant inhibitory effects on cancer cells while maintaining minimal cytotoxicity toward normal cells. It is envisioned that CP-HoMS could serve as an effective and biocompatible platform for the advancement of intelligent drug delivery systems in the realm of cancer therapy.

Prediction of blood–brain barrier penetrating peptides based on data augmentation with Augur

BackgroundThe blood–brain barrier serves as a critical interface between the bloodstream and brain tissue, mainly composed of pericytes, neurons, endothelial cells, and tightly connected basal membranes. It plays a pivotal role in safeguarding brain from harmful substances, thus protecting the integrity of the nervous system and preserving overall brain homeostasis. However, this remarkable selective transmission also poses a formidable challenge in the realm of central nervous system diseases treatment, hindering the delivery of large-molecule drugs into the brain. In response to this challenge, many researchers have devoted themselves to developing drug delivery systems capable of breaching the blood–brain barrier. Among these, blood–brain barrier penetrating peptides have emerged as promising candidates. These peptides had the advantages of high biosafety, ease of synthesis, and exceptional penetration efficiency, making them an effective drug delivery solution. While previous studies have developed a few prediction models for blood–brain barrier penetrating peptides, their performance has often been hampered by issue of limited positive data.ResultsIn this study, we present Augur, a novel prediction model using borderline-SMOTE-based data augmentation and machine learning. we extract highly interpretable physicochemical properties of blood–brain barrier penetrating peptides while solving the issues of small sample size and imbalance of positive and negative samples. Experimental results demonstrate the superior prediction performance of Augur with an AUC value of 0.932 on the training set and 0.931 on the independent test set.ConclusionsThis newly developed Augur model demonstrates superior performance in predicting blood–brain barrier penetrating peptides, offering valuable insights for drug development targeting neurological disorders. This breakthrough may enhance the efficiency of peptide-based drug discovery and pave the way for innovative treatment strategies for central nervous system diseases.

3D Printing Chitosan-based Nanobiomaterials for Biomedicine and Drug Delivery: Recent Advances on the Promising Bioactive Agents and Technologies

Abstract: 3D bioprinting is a novel technology that has gained significant attention recently due to its potential applications in developing simultaneously controlled drug delivery systems (DDSs) for administering several active substances, such as growth factors, proteins, and drug molecules. This technology provides high reproducibility and precise control over the fabricated constructs in an automated way. Chitosan is a natural-derived polysaccharide from chitin, found in the exoskeletons of crustaceans such as shrimp and crabs. Chitosan-based implants can be prepared using 3D bioprinting technology by depositing successive layers of chitosan-based bioink containing living cells and other biomaterials. The resulting implants can be designed to release drugs at a controlled rate over an extended period. The use of chitosan-based implants for drug delivery has several advantages over conventional drug delivery systems. Chitosan is biodegradable and biocompatible, so it can be safely used in vivo without causing any adverse effects. It is also non-immunogenic, meaning it does not elicit an immune response when implanted in vivo. Chitosan-based implants are also cost-effective and can be prepared using simple techniques. 3D bioprinting is an emerging technology that has revolutionized the field of tissue engineering by enabling the fabrication of complex 3D structures with high precision and accuracy. It involves using computer-aided design (CAD) software to create a digital model of the desired structure, which is then translated into a physical object using a 3D printer. The printer deposits successive layers of bioink, which contains living cells and other biomaterials, to create a 3D structure that mimics the native tissue. One of the most promising applications of 3D bioprinting is developing drug delivery systems (DDSs) to administer several active substances, such as growth factors, proteins, and drug molecules. DDSs are designed to release drugs at a controlled rate over an extended period, which can improve therapeutic efficacy and reduce side effects. Chitosan-based implants have emerged as a promising candidate for DDSs due to their attractive properties, such as biodegradability, biocompatibility, low cost, and non-immunogenicity. 3D bioprinting technology has emerged as a powerful tool for developing simultaneously controlled DDSs for administering several active substances. The rationale behind integrating 3D printing technology with chitosan-based scaffolds for drug delivery lies in the ability to produce customized, biocompatible, and precisely designed systems that enable targeted and controlled drug release. This novel methodology shows potential for advancing individualized healthcare, regenerative treatments, and the creation of cutting-edge drug delivery systems. This review highlights the potential applications of 3D bioprinting technology for preparing chitosan-based implants for drug delivery.

State of the Art of Silica Nanoparticles: An Overview on Biodistribution and Preclinical Toxicity Studies.

Over the past few years, nanoparticles have drawn particular attention in designing and developing drug delivery systems due to their distinctive advantages like improved pharmacokinetics, reduced toxicity, and specificity. Along with other successful nanosystems, silica nanoparticles (SNPs) have shown promising effects for therapeutic and diagnostic purposes. These nanoparticles are of great significance owing to their modifiable surface with various ligands, tunable particle size, and large surface area. The rate and extent of degradation and clearance of SNPs depend on factors such as size, shape, porosity, and surface modification, which directly lead to varying toxic mechanisms. Despite SNPs' enormous potential for clinical and pharmaceutical applications, safety concerns have hindered their translation into the clinic. This review discusses the biodistribution, toxicity, and clearance of SNPs and the formulation-related factors that ultimately influence clinical efficacy and safety for treatment. A holistic view of SNP safety will be beneficial for developing an enabling SNP-based drug product.