Drug Delivery Efficacy Research Articles

Engineering Ultra‐Small Cerium‐Based Metal–Organic Frameworks Nanozymes for Efficient Antioxidative Treatment of Dry Eye Disease

AbstractDry eye disease (DED) is a widespread ophthalmic illness that inflicts massive economic and medical burdens on society. Although oxidative stress is closely associated with the onset of DED, barely any quantities of antioxidants are clinically available owing to low efficiency, toxicity, and poor bioavailability. Cerium‐based nanozymes possess promising enzyme‐mimetic activities in scavenging reactive oxygen species (ROS). Moreover, the ultra‐small metal–organic frameworks (MOFs) have the potential for more efficient drug delivery, ROS elimination, and therapeutic efficacy. However, the development of ultra‐small cerium‐based MOFs (Ce‐MOFs) is limited to a small minority due to challenges in the synthetic process and stability. By simply adjusting raw ingredients concentrations, three types of Ce‐MOFs with distinct particle sizes are synthesized: Ce‐MOF 1 (213 nm), Ce‐MOF 2 (36 nm), and Ce‐MOF 3 (2 nm). In comparison, the obtained ultra‐small Ce‐MOF 3 exhibited superior ROS scavenging and antioxidant capacity, decreased cytotoxicity, and excellent ocular penetration. Therapeutically, Ce‐MOF 3 is demonstrated to be highly efficient in alleviating DED by suppressing oxidative stress and inflammation, boosting corneal epithelial repair, and facilitating tear secretion recovery. The novel ultra‐small Ce‐MOF 3 may serve as a promising alternative treatment for DED and other ROS‐related disorders when combined with ocular biocompatibility.

Enhancing the drug delivery efficacy of nanodiamond (C20H22): A DFT-based study of doxorubicin and melphalan interaction on pristine and doped surfaces

In this study, density functional theory calculations were conducted to investigate the interaction and electronic properties of two anti-cancer drugs, doxorubicin and melphalan, using pristine and Cr-doped nanodiamonds. The interaction energies of doxorubicin and melphalan onto pristine nanodiamond were calculated to be −259.584 kJ/mol and −251.286 kJ/mol, respectively, indicating an exothermic process. Doping the nanodiamond with Cr enhanced the interaction, with energies of −297.786 kJ/mol for doxorubicin and −286.694 kJ/mol for melphalan. Chemical hardness, highest occupied molecular orbital, and lowest unoccupied molecular orbital analysis showed that both doped complexes with Cr were relatively soft, with nanodiamond-doxorubicin being softer than nanodiamond-melphalan. The high dipole moment of doped nanodiamond-Cr-doxorubicin 9.979 Debye compared to nanodiamond-doxorubicin 3.989 Debye suggests that doped nanodiamond-doxorubicin is more interaction. Thermodynamic calculations revealed the spontaneity and stability of these complexes. Overall, the results demonstrate the enhanced drug loading capacity of Cr-doped nanodiamonds and their potential as drug delivery carriers for doxorubicin and melphalan.

Enzyme-Silenced Nanosponges Prolong Intratumoral Lifetime to Facilitate Intercellular Relay Drug Delivery and Treatment Efficacy.

The clinical application of nanomedicines faces the dilemma of improved safety but restricted efficacy due to the poor intratumoral bioavailability of chemotherapeutics. We here design an enzyme-silenced nanosponge that shares a long-term lifespan to reversibly exhale/inhale doxorubicin (DOX) for continuous intercellular relay delivery and improved intratumoral retention. The nanosponge is composed of a cationic lipid overlaying a hyaluronic acid derivative polyampholyte core for enveloping of DOX and hyaluronidase-1-targeted siRNA (siHyal1), and a lipoprotein shell decorated with fusion peptide 4F-tLyP-1 that was fused with apolipoprotein A-I (apoA-I) mimetic peptide 4F and tLyP-1 for tumor homing and extravasation into the tumor interstitium. Triggered by the intra/intercellular pH variation, the nanosponge core could reversibly swell in endo/lysosome (pH 5.0) for DOX release. Owing to the deprotonation, the nanosponge core shrinks back in cytoplasm (pH 7.4) for DOX reloading and continues the behavior after being secreted to the extracellular matrix (pH 6.8) via Golgi apparatus, which dramatically improves intratumoral DOX retention and availability. Concurrently, the intratumoral lifespan of the nanosponge is prolonged by siHyal1-specific silencing, ensuring spatiotemporal consistency of carrier and drug when shuttling multilayer tumor cells. As a result, the nanosponge achieves efficient tumor inhibition in 99.1% of tumor spheroids and 80.1% of orthotopic tumor models. Collectively, this study provides an intelligent nanosponge design for active intercellular relay drug delivery, achieving improved intratumoral bioavailability of drugs and amplified chemotherapy on solid tumors.

Brain Delivery of Cisplatin Using Microbubbles in Combination with Ultrasound as an Effective Therapy for Glioblastoma.

Glioblastoma is a highly invasive and fatal disease. Temozolomide, a blood-brain barrier (BBB)-penetrant therapeutic agent currently used for glioblastoma, does not exhibit sufficient therapeutic effect. Cisplatin (CDDP), a versatile anticancer drug, is not considered a therapeutic option for glioblastoma due to its low BBB permeability. We previously investigated the utility of microbubbles (MBs) in combination with ultrasound (US) in promoting BBB permeability and reported the efficacy of drug delivery to the brain using a minimally invasive approach. This study aimed to evaluate the feasibility of CDDP delivery to the brain using the combination of MBs and US for the treatment of glioblastoma. We used mice that were implanted with glioma-261 GFP-Luc cells expressing luciferase as the glioblastoma model. In this model, after tumor inoculation, the BBB opening was induced using MBs and US, and CDDP was simultaneously administered. We found that the CDDP concentrations were higher at the glioblastoma site where the US was applied, although CDDP normally cannot pass through the BBB. Furthermore, the survival was longer in mice treated with CDDP delivered via MBs and US than in those treated with CDDP alone or those that were left untreated. These results suggest that the combination of MBs and US is an effective antitumor drug delivery system based on BBB opening in glioblastoma therapy.

Polyamidoamine dendrimer-mediated hydrogel for solubility enhancement and anti-cancer drug delivery.

The application of hydrogels for anti-cancer drug delivery has garnered considerable interest in the medical field. Current cancer treatment approaches, such as chemotherapy and radiation therapy, often induce severe side effects, causing significant distress and substantial health complications to patients. Hydrogels present an appealing solution as they can be precisely injected into specific sites within the body, facilitating the sustainable release of encapsulated drugs. This localized treatment approach holds great potential for reducing toxicity levels and improving drug delivery efficacy. In this study we developed a hydrogel delivery system containing polyamidoamine (PAMAM) dendrimer and polyethylene glycol (PEG) for solubility enhancement and sustained delivery of hydrophobic anti-cancer drugs. The three selected model drugs, e.g. silibinin, camptothecin, and methotrexate, possess limited aqueous solubility and thus face restricted application. In the presence of vinyl sulfone functionalized PAMAM dendrimer at 45 mg/mL concentration, drug solubility is increased by 37-fold, 4-fold, and 10-fold for silibinin, camptothecin, and methotrexate, respectively. By further crosslinking of the functionalized PAMAM dendrimer and thiolated PEG, we successfully developed a fast-crosslinking hydrogel capable of encapsulating a significant payload of solubilized cancer drugs for sustained release. In water, the drug encapsulated hydrogels release 30%-80% of their loads in 1-4days. MTT assays of J82 and MCF7 cells with various doses of drug encapsulated hydrogels reveal that cytotoxicity is observed for all three drugs on both J82 and MCF7 cell lines after 48h. Notably, camptothecin exhibits higher cytotoxicity to both cell lines than silibinin and methotrexate, achieving up to 95% cell death at experimental conditions, despite its lower solubility. Our experiments provide evidence that the PAMAM dendrimer-mediated hydrogel system significantly improves the solubility of hydrophobic drugs and facilitates their sustained release. These findings position the system as a promising platform for controlled delivery of hydrophobic drugs for intratumoral cancer treatment.

Advances in Therapeutic Contact Lenses for the Management of Different Ocular Conditions.

In the advent of an increasingly aging population and due to the popularity of electronic devices, ocular conditions have become more prevalent. In the world of medicine, accomplishing eye medication administration has always been a difficult task. Despite the fact that there are many commercial eye drops, most of them have important limitations, due to quick clearance mechanisms and ocular barrers. One solution with tremendous potential is the contact lens used as a medication delivery vehicle to bypass this constraint. Therapeutic contact lenses for ocular medication delivery have attracted a lot of attention because they have the potential to improve ocular bioavailability and patient compliance, both with minimal side effects. However, it is essential not to compromise essential features such as water content, optical transparency, and modulus to attain positive in vitro and in vivo outcomes with respect to a sustained drug delivery profile from impregnated contact lenses. Aside from difficulties like drug stability and burst release, the changing of lens physico-chemical features caused by therapeutic or non-therapeutic components can limit the commercialization potential of pharmaceutical-loaded lenses. Research has progressed towards bioinspired techniques and smart materials, to improve the efficacy of drug-eluting contact lenses. The bioinspired method uses polymeric materials, and a specialized molecule-recognition technique called molecular imprinting or a stimuli-responsive system to improve biocompatibility and support the drug delivery efficacy of drug-eluting contact lenses. This review encompasses strategies of material design, lens manufacturing and drug impregnation under the current auspices of ophthalmic therapies and projects an outlook onto future opportunities in the field of eye condition management by means of an active principle-eluting contact lens.

Synergistic anticancer therapy via ferroptosis using modified bovine serum albumin nanoparticles loaded with sorafenib and simvastatin

Ferroptosis is a non-apoptotic cell death pathway characterized by the accumulation of lipid-peroxy radicals within the affected cells. Here, we investigate the synergistic capacity of sorafenib (SOR) and simvastatin (SIM) to trigger ferroptosis for cancer therapy. For precise in-vivo delivery, SOR + SIM was ratiometrically loaded in bovine serum albumin nanoparticles (BSA-NPs) modified with 4-carboxy phenylboronic acid (CPBA). The developed CPBA-BSA(SOR + SIM)-NPs revealed size of 175.2 ± 12.8 nm, with PDI of 0.22 ± 0.03 and Z-potential of −29.6 ± 4.8 mV. Significantly, CPBA-BSA(SOR + SIM)-NPs exhibited > 2 and > 5-fold reduction in IC50 values compared to individual SOR and SIM treatments respectively, in all tested cell lines. Moreover, CPBA-BSA(SOR + SIM)-NPs treated cells exhibited decrease in glutathione levels, increase in malonaldehyde levels and depolarization of mitochondrial membrane potential (JC-1 assay). Pharmacokinetic analysis revealed enhanced AUC0-∞ and MRT levels for SOR and SIM when administered as CPBA-BSA(SOR + SIM)-NPs compared to free drugs. Crucially, in in-vivo experiments, CPBA-BSA(SOR + SIM)-NPs led to a significant reduction in tumor volume compared to various control groups. Histological and biomarker analyses underscore their biocompatibility for clinical applications. In conclusion, this study highlights the potential of CPBA-BSA(SOR + SIM)-NPs as a promising strategy for inducing ferroptosis in cancer cells, concurrently improving drug delivery and therapeutic efficacy. This approach opens new avenues in cancer treatment.

Exploring the potential of transethosomes in therapeutic delivery: A comprehensive review

AbstractThe growing need for innovative drug delivery systems has led to extensive research to address the limitations associated with conventional dosage forms. Lipid nanoparticles have become prominent as frontline nanocarriers for the delivery of drugs and vaccine formulations. However, the pursuit of new materials and modifications to improve lipid nanocarrier properties remains ongoing. In this context, transethosomes have gained attention as a promising solution, offering distinct advantages over traditional formulations. Transethosomes minimize plasma fluctuations, first‐pass metabolism, organ toxicity, and poor bioavailability. This comprehensive review provides an in‐depth exploration of transethosomes, starting with an overview of the impact of formulation components on their properties and effective targeting. This article delves into the production techniques and evaluation properties employed to ensure efficient drug delivery. A significant contribution of this review lies in the analysis of various routes of administration for transethosomes, including transdermal, transvaginal, pulmonary, and ocular delivery, showcasing the versatility of transethosome‐loaded with drugs and their potential to target specific tissues to achieve controlled release. Furthermore, the potential of functionalization and photodynamic therapy approaches to enhance drug delivery efficacy are explored. Overall, this review emphasizes the significant potentiality of transethosomes as a promising drug delivery system addressing the challenges associated with conventional drug delivery approaches.

A mathematical model for maximizing drug uptake in low-EPR tumors using different methods of ultrasound-mediated drug delivery

Cancer remains a significant health burden and research efforts aim to improve drug delivery options. Focused ultrasound has emerged as a potential mechanism for enhanced targeted drug delivery in tumors with a low Enhanced Permeability and Retention (EPR) effect by “sonoporation”. Traditional sonoporation has shown promise, but it can still benefit from improvements in drug uptake. The current study investigates the use of a new non-portative technique, called “ultrasonic tumor painting,” to enhance vascular retention of nanoparticles in the tumor space to achieve targeted drug delivery and increase therapeutic efficacy. An existing mathematical model was adapted to simulate the concentration of free and liposome encapsulated doxorubicin in circulation. The simulations were performed in MATLAB and specifically evaluate doxorubicin uptake in low EPR tumors. To increase drug uptake, sonoporation was employed where efficiency of intratumoral liposomal doxorubicin uptake was increased. An alternative non-permeabilizing strategy, called “tumor painting,” was utilized to improve vascular retention instead of increasing permeability. After retention, the small molecule doxorubicin is allowed to leak into the tumors space via concentration mediated Fickian Diffusion. This study demonstrates that ultrasound-based drug delivery can be improved with tumor painting. This method is a valuable tool to overcome the limitations of traditional sonoporation and has exciting potential for enhancing the therapeutic efficacy of chemotherapy.

Enhancing Transdermal Delivery of Ketorolac Tromethamine Using Dimethyl Sulfoxide: A Systematic Study

Transdermal delivery systems which are directly applied on the skin serve as a substitute for oral drug delivery avoiding first-pass metabolism. The problem of drug penetration through the skin definitely remains one of the biggest issues. This study ascertains the likelihood of DMSO, a penetration enhancer to boost KT, one of the most powerful analgesics. Through DMSO amount variations on KT were prepared and then permeation was studied by means of a Franz Diffusion cell system on rat skin. It increased the permeability coefficient and flux with the increase of the DMSO level, and it reached the maximum when the DMSO concentration was 0. 1. Further understanding of mechanisms and optimal DMSO concentrations seem to be necessary for future development of this promising anticancer treatment approach. Briefly summarizing, DMSO does seem to meet the demands, according to the transdermal drug delivery efficacy standpoint, being safe and convenient for topical application.

Perivascular nanocarrier aggregation as a drug reservoir augments tumor drug delivery and treatment efficacy

Anticancer nanomedicines must overcome a series of physiological and pathological barriers to reach the site of action, and this often leads to low overall therapeutic efficiency. Herein, we present tumor acidity regulated rapid aggregation of nanocarriers around tumor blood vessels to construct drug reservoirs for on-demand drug delivery. We designed two nanocarriers, one that protonates extremely quickly to expose click reactive groups on its surface and that subsequently reacted with the other noncarrier via click chemistry to rapidly form agglomerates as drug reservoirs. In proof-of-concept experiments, vascular disrupting agent combretastatin A4 (CA4) and hypoxia-activated prodrug PR-104A were loaded into the two nanocarriers, respectively. CA4 was enriched near blood vessels while PR-104A diffused deep into tumors and was activated by profound hypoxia levels induced by CA4. This combination produced effective adaptive therapy for tumors with different hypoxia levels.

Polymer–lipid hybrid nanoparticles as potential lipophilic anticancer drug carriers

Nanocarrier systems are widely used for drug delivery applications, but limitations such as the use of synthetic surfactants, leakage of toxic drugs, and a poor encapsulation capacity remain as challenges. We present a new hybrid nanocarrier system that utilizes natural materials to overcome these limitations and improve the safety and efficacy of drug delivery. The system comprises a biopolymeric shell and a lipid core, encapsulating the lipophilic anticancer drug paclitaxel. Bovine serum albumin and dextran, in various molecular weights, are covalently conjugated via Maillard reaction to form the shell which serves as a stabilizer to maintain nanoparticle integrity. The properties of the system, such as Maillard conjugate concentration, protein/polysaccharide molar ratio, and polysaccharide molecular weight, are optimized to enhance nanoparticle size and stability. The system shows high stability at different pH conditions, high drug loading capacity, and effective in vitro drug release through the trigger of enzymes and passive diffusion. Serine proteases are used to digest the protein portion of the nanoparticle shell to enhance the drug release. This nanocarrier system represents a significant advancement in the field of nanomedicine, offering a safe and effective alternative for the delivery of lipophilic drugs.Graphical abstract

Guar-Based Injectable Hydrogel for Drug Delivery and In Vitro Bone Cell Growth.

Injectable hydrogels offer numerous advantages in various areas, which include tissue engineering and drug delivery because of their unique properties such as tunability, excellent carrier properties, and biocompatibility. These hydrogels can be administered with minimal invasiveness. In this study, we synthesized an injectable hydrogel by rehydrating lyophilized mixtures of guar adamantane (Guar-ADI) and poly-β-cyclodextrin (p-βCD) in a solution of phosphate-buffered saline (PBS) maintained at pH 7.4. The hydrogel was formed via host-guest interaction between modified guar (Guar-ADI), obtained by reacting guar gum with 1-adamantyl isocyanate (ADI) and p-βCD. Comprehensive characterization of all synthesized materials, including the hydrogel, was performed using nuclear magnetic resonance (NMR) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and rheology. The in vitro drug release study demonstrated the hydrogel's efficacy in controlled drug delivery, exemplified by the release of bovine serum albumin (BSA) and anastrozole, both of which followed first-order kinetics. Furthermore, the hydrogel displayed excellent biocompatibility and served as an ideal scaffold for promoting the growth of mouse osteoblastic MC3T3 cells as evidenced by the in vitro biocompatibility study.

Hydrogel-Based Formulations for Drug Delivery to the Posterior Segment of the Eye

Hydrogel-based formulations hold significant promise for treating ocular diseases that impact the posterior segment of the eye. These formulations exhibit the ability to surmount ocular barriers and offer sustained drug release, rendering them efficacious drug delivery systems. This article addresses the challenges linked to treating disorders affecting the posterior eye segment and underscores the imperative for less invasive drug delivery methodologies. We further delve into diverse contemporary ocular dosage forms, encompassing gels, nanostructures, and implants, with a specific emphasis on hydrogels. Hydrogels offer several merits, including precise targeting, sustained release, enhanced bioavailability, and non-invasiveness. Moreover, they curtail the risk of adverse effects and foster patient adherence. An enthralling advancement is the amalgamation of hybrid drug delivery systems, integrating nanoparticles, liposomes, dendrimers, and stimuli-activated nano-systems, with hydrogels for posterior eye ailment treatment. These hybrid nano-systems exhibit promise in enhancing drug stability, prolonging drug release, and pinpointing specific tissues within the posterior segment. We also provide an overview of ongoing clinical trials and approved hydrogel-based drug delivery systems, like Retisert and Ozurdex. These systems have demonstrated efficacy in managing chronic non-infectious uveitis, Age-related Macular Degeneration (AMD), and diabetic macular edema. Nevertheless, challenges persist, including optimizing bioavailability, maintaining drug stability, and implementing personalized treatment approaches. The incessant evolution of gel-based drug delivery systems stands to substantially enhance patients’ quality of life and establish new benchmarks in treating posterior eye diseases. The future of ophthalmology brims with excitement, as gel-based drug delivery systems hold the potential to revolutionize ocular therapies, providing effective remedies for an array of vision-related afflictions.

Clinical protocol: Feasibility of evaluating abemaciclib neuropharmacokinetics of diffuse midline glioma using intratumoral microdialysis.

Diffuse midline gliomas (DMG) are the most aggressive brain tumors of childhood and young adults, with documented 2-year survival rates <10%. Treatment failure is due in part to the function of the BBB. Intratumoral microdialysis sampling is an effective tool to determine brain entry of varied agents and could help to provide a better understanding of the relationship of drug permeability to DMG treatment responsivity. This is a non-randomized, single-center, phase 1 clinical trial. Up to seven young adult (18-39 years) patients with recurrent high-grade or diffuse midline glioma will be enrolled with the goal of 5 patients completing the trial over an anticipated 24 months. All patients will take abemaciclib pre-operatively for 4.5 days at twice daily dosing. Patients will undergo resection or biopsy, placement of a microdialysis catheter, and 48 hours of dialysate sampling coupled with timed plasma collections. If intratumoral tumor or brain dialysate sampling concentrations are >10nmol/L, or tumor tissue studies demonstrate CDK inhibition, then restart of abemaciclib therapy along with temozolomide will be administered for maintenance therapy and discontinued with evidence of radiologic or clinical disease progression. The poor survival associated with diffuse midline gliomas underscore the need for improved means to evaluate efficacy of drug delivery to tumor and peritumoral tissue. The findings of this novel study, will provide real-time measurements of BBB function which have the potential to influence future prognostic and diagnostic decisions in such a lethal disease with limited treatment options. Trial registration: Clinicaltrials.gov, NCT05413304. Registered June 10, 2022, Abemaciclib Neuropharmacokinetics of Diffuse Midline Glioma Using Intratumoral Microdialysis.

Intranasal nanoparticulate delivery systems for neurodegenerative disorders: a review.

Neurodegenerative diseases are a significant cause of mortality worldwide, and the blood-brain barrier (BBB) poses a significant challenge for drug delivery. An intranasal route is a prominent approach among the various methods to bypass the BBB. There aredifferent pathways involved in intranasal drug delivery. The drawbacks of this method include mucociliary clearance, enzymatic degradationand poor drug permeation. Novel nanoformulations and intranasal drug-delivery devices offer promising solutions to overcome these challenges. Nanoformulations include polymeric nanoparticles, lipid-based nanoparticles, microspheres, liposomes and noisomes. Additionally, intranasal devices could be utilized to enhance drug-delivery efficacy. Therefore, intranasal drug-delivery systems showpotential for treating neurodegenerative diseases through trigeminal or olfactory pathways, which can significantly improve patient outcomes.

Round Window Niche Veil is Visible on High-Resolution Computed Tomography and a Predictor of Local Drug Efficacy to Inner Ear.

To determine the morphologies and effect of the round window niche veil (RWNV) on local drug delivery efficacy and develop diagnostic criteria on high-resolution computed tomography (HRCT). Patients diagnosed with otosclerosis, bilateral profound sensorineural hearing loss or vestibular schwannoma were enrolled from 2019 to 2022, receiving temporal bone HRCT scanning, and anatomic variations of RWMV were summarized intraoperative. For patients with vestibular schwannoma, 1 mL of dexamethasone solution (4 mg/mL) was administered via facial recess during operation, and samples of perilymph were collected to analyze. The diagnostic criteria of RWNV on HRCT were developed and verified. A total of 85 patients were enrolled. RWNV was observed in 54 cases intraoperatively with an incidence of 63.5% (95% CI, 52.9%-73.0%). The median perilymph concentrations were 4.86-fold higher in the group without RWNV than with RWNV (p < 0.0001). RWNV could be visualized on HRCT with a window width of 3500-4500 HU and a window level of 300-500 HU. The characteristic features were as follows: (1) a thin soft tissue shadow could be seen at the entrance of the round window niche (RWN); (2) it was visible in at least 2 consecutive layers along the upper margin of RWN from top to bottom; (3) it was discontinuous with the adjacent bone margin. The sensitivity and specificity of the diagnostic criteria were 77.8% and 93.6%, respectively. RWNV could reduce local dexamethasone diffusion efficacy to the inner ear, which could be diagnosed on HRCT and used as a predictor of local drug delivery efficacy to the inner ear. 3 Laryngoscope, 134:1396-1402, 2024.

Practicality of non-invasive glucagon-loaded dissolving microneedle for life-saving treatment of severe hypoglycemia in a diabetic rat model

The development of dissolving microneedles (DMNs) has brought light to the transdermal delivery of biomolecules that are released into the skin through the rapid dissolution of the matrix material to enter the systemic circulation and exert therapeutic effects. Herein, we aimed to prepare, characterize, and analyze the effectiveness of a glucagon-loaded DMN system that rapidly increases blood sugar levels in rats with diabetic hypoglycemia. The stability and content of biological drugs following DMNs preparation was assessed using circular dichroism and bicinchoninic acid kit for protein determination kits(BCA kits). The maximum drug loading capacity of DMNs was approximately 140 μg in each patch, and the microneedles could be stored for up to 14 days under dry storage conditions. In vitro skin permeation studies were conducted using a Franz diffusion cell apparatus for glucagon-loaded DMNs. To investigate the efficacy of transdermal drug delivery, drug-laden DMNs were administered to rats with hypoglycemic diabetes. Compared to subcutaneous injections, microneedle drug release demonstrated comparable efficacy in raising blood glucose levels in vivo. Therefore, this study demonstrated that glucagon-loaded DMNs may be a promising approach for efficient transdermal drug delivery as an alternative to subcutaneous injection for the treatment of severe hypoglycemia in patients with diabetes.

Cancer cell membrane-coated bacterial ghosts for highly efficient paclitaxel delivery against metastatic lung cancer

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer, although it is limited by the low tumor delivery efficacy of anticancer drugs. Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect; however, excessively generated immunogenicity will cause serious inflammatory response syndrome. Here, we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts (LP@BG@CCM) by layer-by-layer encapsulation for the treatment of metastatic lung cancer. The preparation processes were simple, only involving film formation, electroporation, and pore extrusion. LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells. In the 4T1 breast cancer metastatic lung cancer mouse models, the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance, the reduced lung weight, the clear lung tissue structure, and the enhanced cancer cell apoptosis compared to its precursors. Moreover, several major immune factors were improved after administration of LP@BG@CCM, including the CD4+/CD8a+ T cells in the spleen and the TNF-α, IFN-γ, and IL-4 in the lung. LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy, which is a promising medication for the treatment of metastatic lung cancer.

An in-depth investigation of the C2 polymer as a next-generation transdermal drug delivery platform

Dermal administration of medications offers high accessibility and convenience for users. Transdermal drug delivery systems (TDDS) have emerged as a promising approach for various applications, including cosmetics, medical purposes, disease treatment, and prevention. While some materials such as hyaluronic acid (HA) and poly(lactic-co-glycolic) acid (PLGA) have been previously investigated for TDDS, our research recently discovered a next-generation material known as the poly(dimethylsilylethylene-dimethylsiloxane) (PDDS) series. Among the PDDS series, the C2 polymer showed high biocompatibility and superior transdermal drug delivery efficacy. In this study, we systematically investigated the C2 polymer and discovered several remarkable attributes. One of the key findings is its high potential for large-scale synthesis. We have demonstrated the biodegradability of the C2 polymer and confirmed that the degradation products derived from the C2 polymer showed negligible toxicity. The C2 polymer also displayed superior skin penetration abilities, allowing for the efficient delivery of hydrophobic and hydrophilic compounds. Our study positions the C2 polymer as a promising next-generation polymeric material for TDDS.