Napabucasin deactivates STAT3 and promotes mitoxantrone-mediated cGAS-STING activation for hepatocellular carcinoma chemo-immunotherapy.

The immune resistance of tumor microenvironment (TME) causes immune checkpoint blockade therapy inefficient to hepatocellular carcinoma (HCC). Emerging strategies of using chemotherapy regimens to reverse the immune resistance provide the promise for promoting the efficiency of immune checkpoint inhibitors. The induction of cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) in tumor cells evokes the adaptive immunity and remodels the immunosuppressive TME. In this study, we report that mitoxantrone (MIT, a chemotherapeutic drug) activates the cGAS-STING signaling pathway of HCC cells. We provide an approach to augment the efficacy of MIT using a signal transducer and activator of transcription 3 (STAT3) inhibitor called napabucasin (NAP). We prepare an aminoethyl anisamide (AEAA)-targeted polyethylene glycol (PEG)-modified poly (lactic-co-glycolic acid) (PLGA)-based nanocarrier for co-delivery of MIT and NAP. The resultant co-nanoformulation can elicit the cGAS-STING-based immune responses to reshape the immunoresistant TME in the mice orthotopically grafted with HCC. Consequently, the resultant co-nanoformulation can promote anti-PD-1 antibody for suppressing HCC development, generating long-term survival, and inhibiting tumor recurrence. This study reveals the potential of MIT to activate the cGAS-STING signaling pathway, and confirms the feasibility of nano co-delivery for MIT and NAP on achieving HCC chemo-immunotherapy.

Potential interventions and interactions of bioactive polyphenols and functional polysaccharides to alleviate inflammatory bowel disease - A review.

Inflammatory bowel disease is a multifaceted condition that is influenced by nutritional, microbial, environmental, genetic, psychological, and immunological factors. Polyphenols and polysaccharides have gained recognition for their therapeutic potential. This review emphasizes the biological effects of polyphenols and polysaccharides, and explores their antioxidant, anti-inflammatory, and microbiome-modulating properties in the management of inflammatory bowel disease (IBD). However, polyphenols encounter challenges, such as low stability and low bioavailability in the colon during IBD treatment. Hence, polysaccharide-based encapsulation is a promising solution to achieve targeted delivery, improved bioavailability, reduced toxicity, and enhanced stability. This review also discusses the significance of covalent and non-covalent interactions, and simple and complex encapsulation between polyphenols and polysaccharides. The administration of these compounds in appropriate quantities has proven beneficial in preventing the development of Crohn's disease and ulcerative colitis, ultimately leading to the management of IBD. The use of polyphenols and polysaccharides has been found to reduce histological scores and colon injury associated with IBD, increase the abundance of beneficial microbes, inhibit the development of colitis-associated cancer, promote the production of microbial end-products, such as short-chain fatty acids (SCFAs), and improve anti-inflammatory properties. Despite the combined effects of polyphenols and polysaccharides observed in both in vitro and in vivo studies, further human clinical trials are needed to comprehend their effectiveness on inflammatory bowel disease.

Recent Advancements in the Delivery of Therapeutic Agents Targeting RNA-dependent RNA Polymerase of SARS-CoV-2.

This study aimed to undertake a complete evaluation and analysis of all known data on RNA-dependent RNA polymerase (RdRp) inhibitors, concentrating on their safety, efficacy, and current improvements in the delivery of therapeutic drugs targeting RdRp of SARS-CoV-2. The work has attempted to emphasise the necessity for future research into the development of nanocarrier-based targeted drug delivery methods for RdRp inhibitors in the treatment of COVID-19. In December 2019, a novel SARS-- CoV-2 strain was discovered in Wuhan, China. SARS-CoV-2 is transferable among humans and has caused a global pandemic. The rapid global outbreak of SARS-CoV-2 and numerous deaths caused because of coronavirus disease (COVID-19) prompted the World Health Organization to announce a pandemic on March 12, 2020. COVID-19 is becoming a key concern that has a significant impact on an individual's life status. RdRp inhibitors are major pharmaceutical agents used in the treatment of COVID-19, which have various undesirable side effects, a greater risk of recurrence, lower bioavailability, as well as a lack of targeted therapy. Hence, the present article has provided a review on all known data on RdRp inhibitors, safety, and efficacy, and recent advances in the delivery of therapeutic agents targeting RdRp of SARS-CoV-2. An analysis has been done using a scientific data search engine, such as the National Center for Biotechnology Information (NCBI/PubMed), Science Direct, Google Scholar, WIPO, Lens, etc. The information has emphasized the need for more research into the safety, efficacy, and development of nanocarrier-based targeted drug delivery systems for RdRp inhibitors in the treatment of COVID-19.

Self-nanoemulsifying drug delivery system for nebulization: fabrication and evaluation for systemic delivery of atorvastatin.

The study undertakes the development of an atorvastatin-loaded self-nanoemulsifying drug delivery system (SNEDDS) to improve its bioavailability. The SNEDDS were fabricated using oleic acid, Tween 80, and Span 80 by spontaneous emulsification. The SNEDDS were assessed for their particle size distribution, zeta potential, morphology, drug content, surface tension, viscosity, and drug release. The aerodynamic performance of the SNEDDS was evaluated using an Andersen cascade impactor, while the lipid-lowering potential of the SNEDDS was determined in Wistar rats using the analyzer "Microlab 300." The particle size of the SNEDDS ranged from 36 to 311 nm, with a polydispersity index (PDI) of 0.25-0.40. The zeta potential of the SNEDDS fluctuated from - 29.22 to - 38.26 mV, which declined to - 4.55 mV in the case of F5. The chitosan-coated formulation (F5) exhibited a higher viscosity (22.12 mPa s) and lower surface tension (0.056 dyne/cm) than other formulations (F1-F4). The non-coated formulation exhibited a significantly higher burst drug release, followed by a sustained drug release pattern (p ≤ 0.05) as compared to the coated formulation (F5). The nebulized SNEDDS achieved a dispersed fraction of 87 to 97%, where notably higher aerosol dispersion from F4 was attributed to its smaller particle size and circularity. The inhaled fraction of nebulized SNEDDS was 74-87%. The size of the SNEDDS droplets was the primary determinant affecting the aerodynamic performance of the SNEDDS during nebulization. The chitosan-coated SNEDDS achieved a higher antihyperlipidemic effect than marketed tablets, which shows the suitability of F5 for effective systemic delivery of atorvastatin through the lung.

2-AG-loaded and bone marrow-targeted PCL nanoparticles as nanoplatforms for hematopoietic cell line mobilization.

BACKGROUND: The use of mobilizing agents for hematopoietic stem cell (HSC) transplantation is insufficient for an increasing number of patients. We previously reported lipid made endocannabinoid (eCB) ligands act on the human bone marrow (hBM) HSC migration in vitro, lacking long term stability to be therapeutic candidate. In this study, we hypothesized if a novel 2-AG-loaded polycaprolactone (PCL)-based nanoparticle delivery system that actively targets BM via phosphatidylserine (Ps) can be generated and validated. METHODS: PCL nanoparticles were prepared by using the emulsion evaporation method and characterized by Zetasizer and scanning electron microscopy (SEM). The encapsulation efficiency and release profile of 2-AG were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The presence of cannabinoid receptors (CBRs) in HSCs and monocytes was detected by flow cytometry. Cell morphology and viability were assessed using transmission electron microscopy (TEM), SEM, and the WST-1 viability assay. The migration efficacy of the 2-AG and 2-AG-loaded nanoparticle delivery system on HSCs and HPSCs (TF-1a and TF-1) and monocytes (THP-1) was evaluated using a transwell migration assay. RESULTS: The 140-225 nm PCL nanoparticles exhibited an increasing polydispersity index (PDI) after the addition of Ps and 2-AG, with a surface charge ranging from - 25 to -50 mV. The nanoparticles released up to 36% of 2-AG within the first 8 h. The 2-AG-Ps-PCL did not affect cellular viability compared to control on days 5 and 10. The HSCs and monocytes expressed CB1R and CB2R and revealed increased migration to media containing 1 µM 2-AG-Ps-PCL compared to control. The migration rate of the HSCs toward monocytes incubated with 1 µM 2-AG-Ps-PCL was higher than that of the monocytes of control. The 2-AG-Ps-PCL formulation provided a real time mobilization efficacy at 1 µM dose and 8 h time window via a specific CBR agonism. CONCLUSION: The newly generated and validated 2-AG-loaded PCL nanoparticle delivery system can serve as a stable, long lasting, targeted mobilization agent for HSCs and as a candidate therapeutic to be included in HSC transplantation (HSCT) protocols following scale-up in vivo preclinical and subsequent clinical trials.

Revolutionizing Brain Drug Delivery: Buccal Transferosomes on the Verge of a Breakthrough.

The buccal cavity, also known as the oral cavity, is a complex anatomical structure that plays a crucial role in various physiological processes. It serves as a gateway to the digestive system and facilitates the initial stages of food digestion and absorption. However, its significance extends beyond mere digestion as it presents a promising route for drug delivery, particularly to the brain. Transferosomes are lipid-based vesicles that have gained significant attention in the field of drug delivery due to their unique structure and properties. These vesicles are composed of phospholipids that form bilayer structures capable of encapsulating both hydrophilic and lipophilic drugs. Strategies for the development of buccal transferosomes for brain delivery have emerged as promising avenues for pharmaceutical research. This review aims to explore the various approaches and challenges associated with harnessing the potential of buccal transferosomes as a means of enhancing drug delivery to the brain. By understanding the structure and function of both buccal tissue and transferosomes, researchers can develop effective formulation methods and characterization techniques to optimize drug delivery. Furthermore, strategic approaches and success stories in buccal transferosome development are highlighted, showcasing inspiring examples that demonstrate their potential to revolutionize brain delivery.

Platelet factors ameliorate thoracic aortic aneurysm and dissection by inhibiting the FGF-FGFR cascade activation in aortic-endothelial cell.

Thoracic aortic aneurysm and dissection (TAAD) is closely associated with vascular endothelial dysfunction. Platelet factor 4 (PF4) is crucial for maintaining vascular endothelial cell homeostasis. However, whether PF4 can influence the progression of TAAD remains unknown. In the present study, we constructed a liposome-encapsulated PF4 nanomedicine and verified its effect on BAPN-induced TAAD in vivo. We found that liposome PF4 nanoparticles (Lipo-PF4), more effectively than PF4 alone, inhibited the formation of TAAD. In vitro, PF4 improved endothelial cell function under pathological conditions by inhibiting migratory and angiogenic abilities of human aortic endothelial cells (HAECs). Mechanically, PF4 inhibited the development of TAAD and improved HAECs function by combining with heparin sulfate and blocking fibroblast growth factor-fibroblast growth factor receptor (FGF-FGFR) signaling. Taken together, we developed a nano-drug (Lipo-PF4) that effectively ameliorates the progression of TAAD by improving endothelial function. Lipo-PF4 is expected to be a therapeutic option for TAAD in the future.

Engineering branched ionizable lipid for hepatic delivery of clustered regularly interspaced short palindromic repeat-Cas9 ribonucleoproteins.

The delivery of the CRISPR/Cas ribonucleoprotein (RNP) has received attention for clinical applications owing to its high efficiency with few off-target effects. Lipid nanoparticles (LNPs) are potential non-viral vectors for the delivery of RNPs. Herein, we report the engineering of a branched scaffold structure of ionizable lipids for the hepatic delivery of RNPs. Both the total carbon number and branching position were critical for the functional delivery of RNPs. The optimal ionizable lipid exhibited a more than 98% reduction in transthyretin protein after a single dose with no obvious signs of toxicity. The mechanistic study has revealed that optimal LNPs have a unique "flower-like structure" that depends on both the lipid structure and the payload and that these LNPs accumulate in hepatocytes in an apolipoprotein E-independent manner. These results represent a major step toward the realization of in vivo genome editing therapy via RNP delivery using chemically synthesizable LNP formulations.

Polylysine in biomedical applications: from composites to breakthroughs.

Polylysine-based composites have emerged as promising materials in biomedical applications due to their versatility, biocompatibility, and tunable properties. In drug delivery, polylysine-based composites furnish a novel platform for targeted and controlled release of therapeutic agents. Their high loading capacity and capability to encapsulate diverse drugs make them ideal candidates for addressing challenges such as drug stability and controlled release kinetics. Additionally, their biocompatibility ensures minimal cytotoxicity, vital for biomedical applications. They also hold substantial potential in tissue engineering by providing a scaffold with tunable mechanical characteristics and surface properties, and can support cell adhesion, proliferation, and differentiation. Furthermore, their bioactive nature facilitates cellular interactions, promoting tissue regeneration and integration. Wound healing is another area where polylysine-based composites show promise. Their antimicrobial properties help prevent infections, while their ability to foster cell migration and proliferation accelerates the wound healing procedure. Incorporation of growth factors or other bioactive molecules further enhances their therapeutic effectiveness. In biosensing applications, they serve as robust substrates for immobilizing biomolecules and sensing elements. Their high surface area-to-volume ratio and excellent biocompatibility improve sensor sensitivity and selectivity, enabling accurate detection of biomarkers or analytes in biological samples. Polylysine-based composites offer potential as contrast agents in bioimaging, aiding in diagnosis and monitoring of diseases. Overall, polylysine-based composites represent a versatile platform with diverse applications in biomedical research and clinical practice, holding great promise for addressing various healthcare challenges. .

Recent advances in targeted drug delivery systems for multiple myeloma.

Despite significant therapeutic advances, multiple myeloma (MM) remains a challenging, incurable, hematological malignancy. The efficacy of traditional chemotherapy and currently available anti-MM agents is in part limited by their adverse effects, which restrict their therapeutic potential. Nanotherapeutics is an emerging field of cancer therapy that can overcome the biological and chemical barriers of existing anticancer drugs. This review presents an overview of recent advancements in nanoparticle- and immunotherapy-based drug delivery systems for MM treatment. It further delves into the targeting strategies, mechanism of controlled drug release, and challenges associated with the development of drug delivery systems for the treatment of MM.

Nanotechnology-Based Drug Delivery Platforms for Erectile Dysfunction: Addressing Efficacy, Safety, and Bioavailability Concerns.

Erectile dysfunction (ED), is a common and multidimensional sexual disorder, which comprises changes among any of the processes of the erectile response such as organic, relational, and psychological. However, both endocrine and nonendocrine causes of ED produce substantial health implications including depression and anxiety due to poor sexual performance, eventually affecting man's life eminence. Marginally invasive interventions following ED consist of lifestyle modifications, oral drugs, injections, vacuum erection devices, etc. Nevertheless, these conventional treatment regimens follow certain drawbacks such as efficacy and safety issues, and navigate to the development of novel therapeutic approaches such as nanomedicine for ED management. Nanotechnology-centred drug delivery platforms are being explored to minimize these limitations with better in vitro and in vivo effectiveness. Moreover, nanomedicine and nanocarrier-linked approaches are rapidly developing science in the nanoscale range, which contributes to site-specific delivery in a controlled manner and has generated considerable interest prominent to their potential to enhance bioavailability, decrease side effects, and avoidance of first-pass metabolism. This review provides an overview of recent discoveries regarding various nanocarriers and nano-delivery methods, along with current trends in the clinical aspects of ED. Additionally, strategies for clinical translation have been incorporated.

Recent advancements of betulinic acid-based drug delivery systems for cancer therapy (2002-2023).

Betulinic acid, a compound classified as a pentacyclic triterpenoid, is found in abundance in a variety of medicinal plants and natural substances. Its broad spectrum of biological and medicinal properties, particularly its potent antitumor activity, has gained significant attention in recent years. The anticancer properties of betulinic acid are governed by mitochondrial signalling pathways and it exhibit selectivity for cancerous tissue, leaving non-cancerous cells and normal tissue unharmed. This characteristic is particularly valuable in chemo-resistant cases. Nevertheless, the medicinal potential of betulinic acid is hindered by its poor water solubility and short half-life, leading to sub-optimal effectiveness. This issue is being tackled by a variety of nano-sized drug delivery systems, such as polymeric nanoparticles, magnetic nanoparticles, polymeric conjugates, nanoemulsions, liposomes, nanosuspensions, carbon nanotubes, and cyclodextrin complexes. This article focuses on recent advances in nanoformulations that are tailored to the delivery of betulinic acid with enhanced effectiveness.

Nanoenabled Antiviral Pesticide for Tobacco Mosaic Virus: Excellent Adhesion Performance and Strong Inhibitory Effect to Alleviate the Damage on Photosynthetic System.

Tobacco mosaic virus (TMV) is a major agricultural threat. Here, a cationic star polymer (SPc) was designed to construct an efficient nanodelivery system for moroxydine hydrochloride (ABOB). ABOB could self-assemble with SPc via a hydrogen bond and van der Waals force, and this complexation reduced the particle size of ABOB from 2406 to 45 nm. With the aid of SPc, the contact angle of ABOB decreased from 100.8 to 79.0°, and its retention increased from 6.3 to 13.8 mg/cm2. Furthermore, the complexation with SPc could attenuate the degradation of ABOB in plants, and the bioactivity of SPc-loaded ABOB significantly improved with a reduction in relative viral expression from 0.57 to 0.17. The RNA-seq analysis revealed that the ABOB/SPc complex could up-regulate the expression of growth- and photosynthesis-related genes in tobacco seedlings, and the chlorophyll content increased by 2.5 times. The current study introduced an efficient nanodelivery system to improve the bioactivity of traditional antiviral agents.

A Combined Phyto- and Photodynamic Delivery Nanoplatform Enhances Antimicrobial Therapy: Design, Preparation, In Vitro Evaluation, and Molecular Docking.

Microbial combating is one of the hot research topics, and finding an alternative strategy is considerably required nowadays. Here, we report on a developed combined chemo- and photodynamic delivery system with a core of zinc oxide nanoparticles (ZnO NPs), porphyrin photosensitizer (POR) connected to alginate polymer (ALG), and berberine (alkaloid natural agent, BER) with favorable antimicrobial effects. According to the achieved main designs, the results demonstrated that the loading capacity and entrapment efficiency reached 22.2 wt % and 95.2%, respectively, for ZnO@ALG-POR/BER nanoformulation (second design) compared to 5.88 wt % and 45.1% for ZnOBER@ALG-POR design (first design). Importantly, when the intended nanoformulations were combined with laser irradiation for 10 min, they showed effective antifungal and antibacterial action against Candida albicans, Escherichia coli, and Staphylococcus aureus. Comparing these treatments to ZnO NPs and free BER, a complete (100%) suppression of bacterial and fungal growth was observed by ZnO@ALG-POR/BER nanoformulation treated E. coli, and by ZnOBER treated C. albicans. Also, after laser treatments, most data showed that E. coli was more sensitive to treatments using nanoformulations than S. aureus. The nanoformulations like ZnOBER@ALG-POR were highly comparable to traditional antibiotics against C. albicans and E. coli before laser application. The results of the cytotoxicity assessment demonstrated that the nanoformulations exhibited moderate biocompatibility on normal human immortalized retinal epithelial (RPE1) cells. Notably, the most biocompatible nanoformulation was ZnOBER@ALG-POR, which possessed ∼9% inhibition of RPE1 cells compared to others. High binding affinities were found between all three microbial strains' receptor proteins and ligands in the molecular docking interaction between the receptor proteins and the ligand molecules (mostly BER and POR). In conclusion, our findings point to the possible use of hybrid nanoplatform delivery systems that combine natural agents and photodynamic therapy into a single therapeutic agent, effectively combating microbial infections. Therapeutic efficiency correlates with nanoformulation design and microorganisms, demonstrating possible optimization for further development.

The Science of Solid Lipid Nanoparticles: From Fundamentals to Applications.

Solid lipid nanoparticles (SLNs) play a crucial role in drug delivery, offering benefits such as enhanced bioavailability, targeted distribution, and reduced toxicity. This article provides a comprehensive overview of SLN formulation, development, and advancement in pharmaceutical research, examining their characteristics, classifications, and significance. The review also delves into the real-world applicability of various SLN formulations across different routes of administration, discussing their advantages, disadvantages, and challenges of scalability, along with strategies for efficient implementation. Furthermore, it explores the diverse applications of SLNs through various delivery methods, addressing the obstacles and potential solutions. By highlighting the critical role of SLNs in improving treatment outcomes, this review underscores their importance in modern drug delivery systems.

Advancements in Colon-Targeted Drug Delivery: A Comprehensive Review on Recent Techniques with Emphasis on Hot-Melt Extrusion and 3D Printing Technologies.

This review investigates the progression and effectiveness of colon-targeted drug delivery systems, offering a comprehensive understanding of the colon's anatomy and physiological environment. Recognizing the distinctive features of the colon is crucial for successfully formulating oral dosage forms that precisely target specific areas in the gastrointestinal tract (GIT) while minimizing side effects through mitigating off-target sites. This understanding forms the basis for designing effective targeted drug delivery systems. The article extensively examines diverse approaches to formulating drugs for colonic targeting, highlighting key polymers and excipients in their production. Special emphasis is given to innovative approaches such as hot-melt extrusion (HME) and three-dimensional printing (3D-P), renowned for their accuracy in drug release kinetics and intricate dosage form geometry. However, challenges arise regarding material standardization and the complex network of regulatory clearances required to confirm safety and effectiveness. The review provides insights into each application's advantages and potential challenges. Furthermore, it sheds light on the local diseases that necessitate colon targeting and the available marketed products, providing an overview of the current state of colon-targeted drug delivery systems. Additionally, the review emphasizes the importance of testing drugs in a controlled in vitro environment during the development phase. It also discusses the future directions for successful development in this field. By integrating knowledge across anatomy, formulation techniques, and assessment methodologies, this review is a valuable resource for researchers navigating the dynamic field of colonic drug delivery.

A combination of lymphatic drug delivery of anti-CTLA-4 antibody and local radiotherapy for solid-tumor treatment.

The combination of radiotherapy and immunotherapy is a promising approach that has been shown in clinical trials to improve significantly survival and response rates compared with monotherapy against solid tumor. Since anti-CTLA-4 antibodies block immunosuppressive signals mainly in the lymph nodes (LNs), efficient drug delivery to the lymphatic system is desirable. However, the immune checkpoint inhibitors, especially anti-CTLA-4 are currently administered intravenously (i.v.), resulting in limited efficacy in controlling solid tumor and inhibiting metastases, and the method of administration has not been optimized. Here, we show that a combination of local radiotherapy and administration of anti-CTLA-4 antibodies using a lymphatic drug delivery system (LDDS) suppresses solid tumor and metastases. We compared the efficacy of LDDS-based immunotherapy or radioimmunotherapy with i.v. administration in a solid-tumor model created by subcutaneous inoculation into LN-swollen mice with osteosarcoma cells. Tumor-bearing mice were divided into various groups (no treatment, immunotherapy [i.v. or LDDS], radiotherapy, and radioimmunotherapy [i.v. or LDDS]) and were observed for 28 days. Immunotherapy was administered with a cumulative dose of 10 mg/kg of anti-CTLA-4 monoclonal antibody, and radiotherapy was administered with a cumulative 8 Gy of fractionated X-ray irradiation. For immunotherapy alone, LDDS provided slight tumor growth inhibition but did not inhibit distant metastasis. For radioimmunotherapy, however, tumor growth was delayed and distant metastasis was suppressed compared with radiotherapy alone. In particular, the LDDS group achieved a high tumor-suppressive effect with T cell-mediated immune activity, indicating the efficacy of LDDS in radioimmunotherapy.

Prodrug Nanomedicine for Synovium Targeted Therapy of Inflammatory Arthritis: Insights from Animal Model and Human Synovial Joint Fluid.

Many patients cannot tolerate low-dose weekly methotrexate (MTX) therapy for inflammatory arthritis treatment due to life-threatening toxicity. Although biologics offer a target-specific therapy, it raises the risk of serious infections and even cancer due to immune system suppression. We introduce an anti-inflammatory arthritis MTX ester prodrug using a long-circulating biocompatible polymeric macromolecule: folic acid (FA) functionalized hyperbranched polyglycerol (HPG). In vitro the drug MTX is incrementally released through pH and enzymatic degradation over 2 weeks. The role of matrix metalloproteinases (MMPs) in site-specific prodrug activation was verified using synovial fluid (SF) of 26 rheumatology patients and 4 healthy controls. Elevated levels of specific MMPs-markers of joint inflammation-positively correlated with enhanced prodrug release explained by acid-catalyzed hydrolysis of esters by proteases. Intravenously administered 111In-radiolabeled prodrug confirmed by SPECT/CT imaging that it accumulated preferentially in inflamed joints while reducing off-target side-effects in a mouse model of rheumatoid arthritis (RA). Added FA as a targeting vector prolonged prodrug action; prodrug with 4x less MTX applied every 2 weeks was as effective as weekly MTX therapy. The preclinical results suggest a prodrug-based strategy for the treatment of inflammatory joint diseases, with potential for other chronic inflammatory diseases and cancer.

Cetuximab-conjugated sodium selenite nanoparticles for doxorubicin targeted delivery against MCF-7 breast cancer cells.

Aim: To develop and characterize doxorubicin-loaded sodium selenite nanoparticles (SSNP-DOX) and their surface attachment with cetuximab (mAb-SSNP-DOX).Methods: SSNP-DOX was formulated by gelation and then conjugated with cetuximab to form mAb-SSNP-DOX. Characterization included DLS, SEM, TEM, DSC, Raman spectroscopy and XRD. In vitro, the kinetics of doxorubicin release and cytotoxicity in MCF-7 breast cancer cells were investigated.Results: The zeta potential for SSNP-DOX and mAb-SSNP-DOX was -14.4 ± 10.1 mV and -27.5 ± 7.28 mV, with particle sizes of 181.3 nm and 227.5 nm, respectively. The formulation intensity was 89.7% for SSNP-DOX and 100% for mAb-SSNP-DOX, with PDI values of 0.419 and 0.251, respectively. SEM and TEM showed that mAb-SSNP-DOX was smooth and spherical. The DSC analysis revealed exothermic peaks at 102.44°C for SSNP-DOX and 144.21°C for mAb-SSNP-DOX, along with endothermic peaks at 269.19°C and 241.6°C, respectively. Raman spectroscopy showed a higher intensity for mAb-SSNP-DOX. The XRD study showed different peaks for each formulation. Both followed zero order kinetics for doxorubicin release. Cytotoxicity studies showed significant effects and high apoptosis in MCF-7 cells for both formulations.Conclusion: The mAb-SSNP-DOX showed promising properties, more effective doxorubicin release and higher cytotoxicity against breast cancer cells compared with SSNP-DOX.

[Box: see text].

Microfabrication of controlled release osmotic drug delivery systems assembled from designed elements.

BACKGROUND: This study investigates combining 3D printing with traditional compression methods to develop a multicomponent, controlled-release drug delivery system (DDS). The system uses osmotic tablet layers and a semipermeable membrane to control drug release, similar to modular Lego® structures. METHODS: The DDS comprises two directly compressed tablet layers (push and pull) and a semipermeable membrane, all contained within a 3D-printed frame. The membrane is made from cellulose acetate and plasticizers like glycerol and propylene glycol. Various characterization techniques, including Positron Annihilation Lifetime Spectroscopy (PALS), were employed to evaluate microstructural properties, wettability, morphology, and drug dissolution. RESULTS: Glycerol improved the membrane's wettability, as confirmed by PALS. The system achieved zero-order drug release, unaffected by stirring rates, due to the push and pull tablets within the 3D-printed frame. The release profile was stable, demonstrating effective drug delivery control. CONCLUSION: The study successfully developed a prototype for a controlled-release osmotic DDS, achieving zero-order release kinetics for quinine hydrochloride after 2 h. This modular approach holds potential for personalized therapies in human and veterinary medicine, allowing customization at the point of care.