Dual-phase release finasteride-loaded microspheres for androgenetic alopecia treatment: rapid intervention and sustained control of dihydrotestosterone.

The core pathogenesis of androgenetic alopecia (AGA) involves abnormal accumulation of dihydrotestosterone (DHT) within hair follicles. However, while existing oral formulations achieve DHT suppression, their delayed clinical efficacy (3-6 months for visible regrowth) fails to meet the need for early intervention. Additionally, the frequent dosing further compromises sustained DHT control through drug-level fluctuations and adherence challenges, enabling local regeneration.

Irinotecan and dexamethasone prodrug co-loaded liposomes for the treatment of breast cancer.

Cancer is a major global health challenge, which has a serious impact on human health and life. While Irinotecan (IRI) has been demonstrated to treat various cancers with remarkable efficacy, addressing its associated side effects remains a critical concern in clinical. Chemotherapy drugs are often used in combination with dexamethasone (DEX) in clinical practice to reduce their side effects.

Oxygen-Generating Transdermal Nanoplatform Codelivering BRD4 Proteolysis-Targeting Chimera/Verteporfin/CaO Synergistically Remodels Immunosuppressive Melanoma Microenvironment to Potentiate Combination Immunotherapy.

Melanoma relapse and metastasis remain formidable clinical challenges, with the inadequate immunogenicity and highly immunosuppressive tumor microenvironment (ITME) presenting serious obstacles to current postsurgical immunotherapies. Herein, an oxygen self-supplying core-shell microneedle patch (AV@LDL&CaO MNs) featuring multiple innovative anticancer therapies and multimodal immunomodulatory properties is developed to facilitate melanoma postoperative management. Specifically, recombinant low-density lipoprotein nanoparticles (AV@LDL NPs) embedding both the bromodomain containing protein 4 (BRD4)-targeting proteolysis-targeting chimera (PROTAC) ARV825 and the photosensitizer verteporfin are strategically incorporated into the dissolvable shell, while the oxygen-generating nanoreactor (HA@CaO NPs) occupies the core compartment.

Harnessing the apical sodium-dependent bile acid transporter for enhanced oral delivery of peptide drugs: mechanisms, strategies, and therapeutic potential.

Introduction: Oral administration of peptide drugs (PDs) faces significant challenges due to the harsh gastrointestinal environment and low intestinal epithelial permeability, leading to poor bioavailability. Current intestinal delivery pathways are often constrained by limited intestinal transport efficiency, which further hinders the effective delivery of PDs. The apical sodium-dependent bile acid transporter (ASBT) presents a promising target for enhancing the oral delivery of PDs.

On-call Mito-Firefighter: Dual-activated nanoparticles based on carboxymethyl chitosan/β-cyclodextrin to achieve mitochondria targeting and destruction/PTT/PDT cascade anticancer treatment.

Indocyanine green (ICG) demonstrates both photodynamic therapy (PDT) and photothermal therapy (PTT) capabilities but faces challenges including rapid blood clearance, insufficient ROS production, and molecular chaperone-induced thermotolerance. However, highly efficient synchronous targeting delivery of photosensitizer and sensitizer to cancer cells remains a giant challenge due to their significantly different physicochemical properties. To address these limitations, we developed a dual-responsive nano-platform, TCS-βCD@CLRP/PEI-SS@ICG-NPs (I&C-NPs), designed for ICG and chloramphenicol (CLRP) co-delivery and cascade synergetic anti-tumor effect through mitochondrial destruction/photothermal therapy/photodynamic therapy (Mito destruction/PTT/PDT).

The self-assembled cabazitaxel-carboxymethylcellulose-mPEG polymer micelles for efficient antitumor activity and low systemic toxicity.

Cabazitaxel (CTX) has emerged as a significant chemotherapeutic drug. However, its poor hydrophilicity and adverse side effects limit its clinical application. In this study, we propose the preparation of self-assembled cabazitaxel-carboxymethylcellulose-mPEG polymer micelles (CTX-CMC-mPEG micelles).

Thermosensitive microemulsion gel incorporating nano-ZnO and black soybean tar improves treatment adherence and alleviates psoriasis-like skin disease.

Tar has been used as a natural product in the treatment of psoriasis for thousands of years and has achieved good clinical therapeutic effects. This study aimed to develop black soybean tar (BST)-zinc oxide (ZnO) composite thermosensitive microemulsion gels (BST-ZnO-MBGs) to improve the properties of BST, increase patient compliance, and enhance drug treatment effects. BST-ZnO20/500/3000-MBGs containing different sizes of ZnO were prepared by high pressure homogenization technology, and the rheology, zinc ion release and transdermal mechanism of the gels were studied.

Integrity of polymeric micelles regulates bioavailability of cyclosporine A: A FRET-based analysis during oral delivery.

This study comprehensively investigated the effect of structural integrity on the oral delivery efficacy of mPEG-b-PCL polymeric micelles (PMs) using fluorescence resonance energy transfer (FRET) technology. During mucus penetration, the integrity loss of PMs resulted from the "hydration effect" of mucins and the "solubilization effect" of bile salts. Increasing surface PEG density or decreasing particle size <50 nm resisted the "hydration effect", while shortening PCL chain or increasing aggregation number alleviated the "solubilization effect".

Linoleic acid co-administration promotes oral delivery of exenatide-loaded butyrate-decorated nanocapsules.

Epithelial cell entrance and trans-epithelial transport are two essential processes that directly affect the efficacy of oral delivery of nanocarriers. Herein, a hydroxyethyl starch-based nanocapsule dual decorated with butyrate and octadecylamine (ODA) was first constructed to enhance transporter-mediated endocytosis and trans-epithelial transport, while reducing exenatide (EXT) loss during absorption. The epithelial barrier was then treated with linoleic acid (LA), which functioned as a cell membrane fluidity regulator.

Precision-targeted explosion of biomimetic nanoparticles for the effective treatment of uveal melanoma.

Uveal melanoma (UM) is the most prevalent primary intraocular malignancy in adults, originating from the melanocytes within the uvea. Currently, the treatment of ocular tumors predominantly relies on conventional approaches such as brachytherapy and enucleation. Despite the limited pharmaceutical treatment options for uveal melanoma (UM), the effectiveness of ocular drug delivery is hindered by the ocular barrier to local drug administration and the complex tumor microenvironment (TME).

Baicalein nanoemulsion in situ GEL for dry age-related macular degeneration.

Effective management of posterior ocular segment disorders necessitates sustained retinal drug delivery and rational therapeutic selection. Despite significant advances, developing drug delivery systems that simultaneously achieve deep tissue penetration and prolonged ocular surface retention remains challenging. To bridge this gap, we engineered a borneol- decorated baicalein nanoemulsion in-situ gel (Bor/Bai-N@GEL) ophthalmic formulation for dry age-related macular degeneration (d-AMD).

Prolonged local retention of vancomycin achieved by a multivesicular liposomes in thermoresponsive gel system for the prevention and treatment of intervertebral disc infection.

The therapeutic efficacy of intervertebral disc (IVD) infections treated with intravenous vancomycin (VCM) is often limited by inadequate blood supply to the IVD. In this study, we developed a localized and sustained-release drug delivery system for the intradiscal administration of VCM. First, VCM-loaded multivesicular liposomes (VCM-MVLs) were prepared using a two-step emulsification process, and we investigated the effects of the preparation process and formulation composition on the quality of the MVLs.

pH-responsive ZIF-8 nanoplatform co-loaded with DSF and ICG for multiple synergistic antitumor therapy.

Disulfiram (Allensworth et al.), an "old drug" for the treatment of chronic alcohol dependence, has received extensive attention due to its potential antitumor activity for new medical applications. However, the application of DSF in cancer therapy was limited by its extremely terrible solubility in water.

Chitosan based surface modulation of core-shell nanoparticles for oral delivery of exenatide via balancing mucus penetration and cellular uptake.

Oral delivery of peptide and protein drugs (PDs) is hindered by the impermeable intestinal mucosa, which consists of both the mucus layer and the epithelium. Therefore, double-layer (mucus layer and epithelium) overcoming nanocarriers need to be designed to enhance the transporting efficiency of PDs. However, the requirements for surface properties to penetrate these two barriers are quite distinct.

Modulating the elasticity of milk exosome-based hybrid vesicles to optimize transepithelial transport and enhance oral peptide delivery.

To address challenges such as limited loading capacity, restricted targeting precision, and low yield of natural exosomes as drug carriers, the fusion of liposomes and exosomes to create hybrid vesicles has emerged as a viable solution approach. While current research mainly focuses on designing functionalized liposomes, less attention is given to how liposome membrane materials affect the elasticity of these hybrids and their delivery efficiency. This study utilized milk exosomes (mExos) as model exosomes, and generated hybrid vesicles with varying elasticity through the fusion of phospholipids with differing chain lengths, examining the disparities among various hybrid vesicles in their ability to overcoming the gastrointestinal barriers.

Characteristics of Tylvalosin Tartrate Enteric Amorphous Pellets Prepared by Liquid Layering.

Purpose: Tylvalosin Tartrate (TAT), a new-generation macrolide antibiotic, undergoes significant degradation in the stomach and in vivo rapid elimination upon oral administration, resulting in poor bioavailability. This study developed TAT enteric amorphous pellets by liquid layering (TAT/EAP-LL) with pH-sensitive and burst release characteristics, to enhance drug stability in the stomach and concentration enrichment in the duodenum.

Methods: The drug loading layer, isolation layer and enteric layer were formed on the surface of the blank core pellets.

Lactoferrin-functionalized PEGylation liposomes loaded with norcantharidin acid for targeted therapy of hepatocellular carcinoma.

Norcantharidin (NCTD), an antitumor agent with an increased leukocyte function, has been used for the treatment of hepatocellular carcinoma (HCC) in clinical. However, the clinical application of NCTD is limited due to its inadequate hydrophilicity and lipophilicity, short half-life (t), as well as adverse effects such as vascular irritation, cardiotoxicity, and nephrotoxicity. Herein, a lactoferrin (Lf) and DSPE-mPEG functionalized liposomes loaded with norcantharidic acid (NCA), an active metabolite of NCTD, was constructed for the targeted therapy of HCC.

Improved epirubicin delivery selectivity to bladder cancer achieved by functionalized hydroxyethyl starch-based prodrug.

Bladder instillation of chemo-therapeutic agents is common for bladder cancer (BC) treatment, however, due to the poor tissue selectivity of chemotherapeutic agents, this method suffers from bladder irritation or even chemical cystitis. Here, we designed a hydroxyethyl starch-based prodrug for epirubicin (EPI) using a pH-sensitive hydrazone linker and folate as the active targeting moiety (FA-HES-hyd-EPI) to achieve delivery selectivity. Prodrug micelles decorated with FA (FA-m), with diameter of 203.

The journey of nanoparticles in the abdominal cavity: Exploring their in vivo fate and impact factors.

Peritoneal carcinomatosis (PC) is caused by metastasis of primary tumor cells from intra-abdominal organs to the peritoneal surface. Intraperitoneal (IP) chemotherapy allows close contact of high concentrations of therapeutic agents with cancer cells in the peritoneal cavity to prolong patient survival. However, conventional IP chemotherapy is prone to rapid elimination from the peritoneal cavity and lacks specificity towards cancer cells.

Novel Sustained Release Azithromycin Resinate Fabricated by One-Pot Ion-exchange Performed in Hydro-alcoholic Solution.

Drug-resin complexes usually form in the aqueous phase. For poorly water-soluble drugs, low drug loading limits the use of resin in drug formulation. In this study, we used a new method to prepare azithromycin resinates, improving the drug loading rate, shortening the preparation time and simplifying the process.

Sodium glycocholate liposome encapsulated semaglutide increases oral bioavailability by promoting intestinal absorption.

The aim of this study was to prepare sodium glycocholate liposomes (SGC-Lip) encapsulating semaglutide (Sml) to improve oral bioavailability and better exert hypoglycemic effect. In this paper, SGC-Lip was prepared by reverse-phase evaporation method with particle size around 140 nm, potential around -27 mV, rounded morphology and better stability. The hypoglycemic and intestinal uptake effects of SGC-Lip and cholesterol-containing liposomes (CH-Lip) were comparatively investigated in rats, and the oral safety of SGC-Lip was examined by cytotoxicity assay.

Redox-sensitive disulfide-bridged self-assembled nanoparticles of dexamethasone with high drug loading for acute lung injury therapy.

Acute lung injury (ALI) arises from an excessive inflammatory response, usually progressing to acute respiratory distress syndrome (ARDS) if not promptly addressed. There is currently a limited array of effective treatments available for ALI. In this study, we developed disulfide bond-bridged prodrug self-assembled nanoparticles (referred to as DSSS NPs).

Milk Exosome-Liposome Hybrid Vesicles with Self-Adapting Surface Properties Overcome the Sequential Absorption Barriers for Oral Delivery of Peptides.

Milk exosomes (mExos) have demonstrated significant promise as vehicles for the oral administration of protein and peptide drugs owing to their superior capacity to traverse epithelial barriers. Nevertheless, certain challenges persist due to their intrinsic characteristics, including suboptimal drug loading efficiency, inadequate mucus penetration capability, and susceptibility to membrane protein loss. Herein, a hybrid vesicle with self-adaptive surface properties (mExos@DSPE-Hyd-PMPC) was designed by fusing functionalized liposomes with natural mExos, aiming to overcome the limitations associated with mExos and unlock their full potential in oral peptide delivery.

Glucocorticoids-based prodrug design: Current strategies and research progress.

Attributing to their broad pharmacological effects encompassing anti-inflammation, antitoxin, and immunosuppression, glucocorticoids (GCs) are extensively utilized in the clinic for the treatment of diverse diseases such as lupus erythematosus, nephritis, arthritis, ulcerative colitis, asthma, keratitis, macular edema, and leukemia. However, long-term use often causes undesirable side effects, including metabolic disorders-induced Cushing's syndrome (buffalo back, full moon face, hyperglycemia, etc.), osteoporosis, aggravated infection, psychosis, glaucoma, and cataract.