Breath and Beyond: Advances in Nanomedicine for Oral and Intranasal Aerosol Drug Delivery.

Designing and standardizing drug formulations are crucial for ensuring the safety and efficacy of medications. Nanomedicine utilizes nano drug delivery systems and advanced nanodevices to address numerous critical medical challenges. Currently, oral and intranasal aerosol drug delivery (OIADD) is the primary method for treating respiratory diseases worldwide.

Investigation of Factors Influencing the Effectiveness of Deformable Nanovesicles for Insulin Nebulization Inhalation.

Nebulized inhalation offers a noninvasive method for delivering drugs to treat both local respiratory and systemic diseases. In this study, insulin was used as a model drug to design a series of deformable nanovesicles (DNVs) with key quality attributes, including particle size, deformability, and drug load capacity. We investigated the effects of these properties on aerosol generation, macrophage phagocytosis, and bloodstream penetration.

Unlocking the potential of amorphous calcium carbonate: A star ascending in the realm of biomedical application.

Calcium-based biomaterials have been intensively studied in the field of drug delivery owing to their excellent biocompatibility and biodegradability. Calcium-based materials can also deliver contrast agents, which can enhance real-time imaging and exert a Ca-interfering therapeutic effect. Based on these characteristics, amorphous calcium carbonate (ACC), as a brunch of calcium-based biomaterials, has the potential to become a widely used biomaterial.

Pharmacokinetics and tissue distribution of Ramulus Mori (Sangzhi) alkaloids in rats and its effects on liver enzyme activity.

Ramulus Mori (Sangzhi) alkaloids (SZ-A) derived from twigs of mulberry ( L., genus in the Moraceae family) was approved by the National Medical Products Administration in 2020 for the treatment of type 2 diabetes mellitus. In addition to excellent hypoglycemic effect, increasing evidence has confirmed that SZ-A exerts multiple pharmacological effects, such as protecting pancreatic -cell function, stimulating adiponectin expression, and alleviating hepatic steatosis.

Tumor-targeting intravenous lipid emulsion of paclitaxel: Characteristics, stability, toxicity, and toxicokinetics.

Lipid nanoemulsions are promising nanodrug delivery carriers that can improve the efficacy and safety of paclitaxel (PTX). However, no intravenous lipid emulsion of PTX has been approved for clinical treatment, and systemic safety profiles have not yet been reported. Here we outline the development of a PTX-loaded tumor-targeting intravenous lipid emulsion (PTX Emul) and describe its characteristics, colloidal stability, and systemic safety profiles in terms of acute toxicity, long-term toxicity, and toxicokinetics.

Deformable Nanovesicle-Loaded Gel for Buccal Insulin Delivery.

Deformable nanovesicles (DNVs) have been widely used in oral mucosal delivery studies of biomolecular drugs. However, their development for oral mucosal preparations has been limited by their physical and chemical instability, the need for small oral volumes, and the complexity of the oral microenvironment. This study aimed to develop a more suitable buccal delivery system for DNVs with improved storage stability.

Research on Transfer Rate of Heavy Metals and Harmful Elements in Traditional Chinese Medicine Extraction and Refining Processes and Product Health Risk Assessment.

Ramulus Mori alkaloids, also known as SangZhi alkaloids (SZ-A), is a natural medicine used for the treatment of type 2 diabetes mellitus in China. SZ-A is extracted from Morus alba L., which grows in the natural environment and may be contaminated by heavy metals and harmful elements.

Comparative colloidal stability, antitumor efficacy, and immunosuppressive effect of commercial paclitaxel nanoformulations.

Background: Standard chemotherapy with taxanes, such as paclitaxel (PTX), remains the mainstay of systemic treatment of triple-negative breast cancer. Nanotechnology-based formulations have gradually replaced PTX injection and are widely used in China. However, no studies have compared the colloidal stability, antitumor efficacy, and safety of commercial PTX nanoformulations.

Improved Safety and Anti-Glioblastoma Efficacy of CAT3-Encapsulated SMEDDS through Metabolism Modification.

13-()-3-pivaloyloxyl-6,7-dimethoxyphenanthro(9,10-)-indolizidine (CAT3) is a novel oral anti-glioma pro-drug with a potent anti-tumor effect against temozolomide-resistant glioma. 13()-3-hydroxyl-6,7-dimethoxyphenanthro(9,10-)-indolizidine (PF403) is the active in vivo lipase degradation metabolite of CAT3. Both CAT3 and PF403 can penetrate the blood-brain barrier to cause an anti-glioma effect.

Comparative study of mucoadhesive and mucus-penetrative nanoparticles based on phospholipid complex to overcome the mucus barrier for inhaled delivery of baicalein.

Efficient mucosal delivery remains a major challenge for the reason of the respiratory tract mucus act as a formidable barrier to nanocarriers by trapping and clearing foreign particulates. The surface property of nanoparticles determines their retention and penetration ability within the respiratory tract mucus. However, the interaction between nanoparticles and mucus, and how these interactions impact distribution has not been extensively investigated.

Factors affecting the buccal delivery of deformable nanovesicles based on insulin-phospholipid complex: an investigation.

Deformable nanovesicles (DNVs) have been used in the buccal delivery of biomacromolecules due to their ability to enhance drug penetration. However, no breakthroughs have been made until now due to limited understanding of the factors affecting buccal delivery. In this study, we designed a series of DNVs, based on an insulin-phospholipid complex (IPC-DNVs), to investigate the influence of drug dose, buccal administration methods, and key quality characteristics of IPC-DNVs for buccal delivery.

Improving the Oral Bioavailability of an Anti-Glioma Prodrug CAT3 Using Novel Solid Lipid Nanoparticles Containing Oleic Acid-CAT3 Conjugates.

13a-(S)-3-pivaloyloxyl-6,7-dimethoxyphenanthro(9,10-b)-indolizidine (CAT3) is a novel oral anti-glioma pro-drug with a potent anti-tumor effect against temozolomide-resistant glioma in vivo. However, poor lipid solubility has limited the encapsulation efficacy during formulation development. Moreover, although the active metabolite of CAT3, 13a(S)-3-hydroxyl-6,7-dimethoxyphenanthro(9,10-b)-indolizidine (PF403), can penetrate the blood-brain barrier and approach the brain tissue with a 1000-fold higher anti-glioma activity than CAT3 in vitro, its bioavailability and C were considerably low in plasma, limiting the anti-tumor efficacy.

Stabilization of Deformable Nanovesicles Based on Insulin-Phospholipid Complex by Freeze-Drying.

Deformable nanovesicles have been extensively investigated due to their excellent ability to penetrate biological barriers. However, suffering from serious physical and chemical instabilities, the wide use of deformable nanovesicles in medical applications is still limited. Moreover, far less work has been done to pursue the lyophilization of deformable nanovesicles.

Drug-free mannosylated liposomes inhibit tumor growth by promoting the polarization of tumor-associated macrophages.

Tumor-associated macrophages (TAMs) are critical in tumor progression and metastasis. Selective targeting of TAMs holds great potential to ameliorate the immunosuppressive tumor microenvironment and enhance the efficacy of antitumor therapy. Various liposomes have been developed to target TAMs via cell-specific surface receptors either to deplete or re-educate TAMs.

Investigation on the Enzymatic Profile of Mulberry Alkaloids by Enzymatic Study and Molecular Docking.

α-glucosidase inhibitors (AGIs) have been an important category of oral antidiabetic drugs being widely exploited for the effective management of type 2 diabetes mellitus. However, the marketed AGIs not only inhibited the disaccharidases, but also exhibited an excessive inhibitory effect on α-amylase, resulting in undesirable gastrointestinal side effects. Compared to these agents, Ramulus Mori alkaloids (SZ-A), was a group of effective alkaloids from natural L.

Mechanisms of deformable nanovesicles based on insulin-phospholipid complex for enhancing buccal delivery of insulin.

Background: Non-injectable delivery of peptides and proteins are not feasible due to its large molecular, high hydrophilic and gastrointestinal degradation. Therefore, proposing a new method to solve this problem is a burning issue.

Purpose: The objective of this study was to propose a novel protein delivery strategy to vanquish the poor efficacy of buccal mucosa delivery systems for protein delivery and then investigate the detailed mechanisms of the enhanced buccal delivery of protein, using insulin as a model drug.

Sequential delivery of VEGF siRNA and paclitaxel for PVN destruction, anti-angiogenesis, and tumor cell apoptosis procedurally via a multi-functional polymer micelle.

Co-delivery of chemotherapy drugs and VEGF siRNA (siVEGF) to control tumor growth has been a research hotspot for improving cancer treatment. Current systems co-deliver siVEGF and chemo drugs into tumor cells simultaneously. Although effective, these systems do not flow to the abnormal blood vessels around tumor cells (vascular niche, PVN), which play an important role in the metastasis and deterioration of the tumor.

Prediction of a Therapeutic Dose for Buagafuran, a Potent Anxiolytic Agent by Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling Starting from Pharmacokinetics in Rats and Human.

Physiologically based pharmacokinetic (PBPK)/pharmacodynamic (PD) models can contribute to animal-to-human extrapolation and therapeutic dose predictions. Buagafuran is a novel anxiolytic agent and phase I clinical trials of buagafuran have been completed. In this paper, a potentially effective dose for buagafuran of 30 mg t.

Pharmacokinetics, Tissue Distribution, and Elimination of Three Active Alkaloids in Rats after Oral Administration of the Effective Fraction of Alkaloids from Ramulus Mori, an Innovative Hypoglycemic Agent.

In this study, we systematically investigated the plasma pharmacokinetics, tissue distribution, and elimination of three active alkaloids after oral administration of the effective fraction of alkaloids from (SZ-A)-an innovative hypoglycemic agent-in rats. Moreover, the influences of other components in SZ-A on dynamic process of alkaloids were explored for the first time. The results showed that 1-deoxynojirimycin (DNJ), fagomine (FGM) and 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) exhibited nonlinear pharmacokinetics following oral administration of SZ-A (40-1000 mg/kg).

Vitamin E-rich Nanoemulsion Enhances the Antitumor Efficacy of Low-Dose Paclitaxel by Driving Th1 Immune Response.

Purpose: To overcome the drawbacks of high dose regimen and improve the outcomes of chemotherapy at a low dose, an immunotherapeutic nanoemulsion based combination of chemotherapeutic agent (paclitaxel) with immunomodulatory agent (vitamin E) was developed and evaluated for their antitumor effect against breast cancer.

Methods: A total of five nanoemulsions loaded with various content of vitamin E were prepared and characterized. The immunoregulatory effects of vitamin E along with the overall antitumor efficacy of vitamin E-rich nanoemulsion with a low dose of paclitaxel were investigated through in vitro and in vivo experiments.

Purification of Houttuynia cordata Thunb. Essential Oil Using Macroporous Resin Followed by Microemulsion Encapsulation to Improve Its Safety and Antiviral Activity.

Essential oil extracted from Thunb. () is widely used in traditional Chinese medicine due to its excellent biological activities. However, impurities and deficient preparations of the essential oil limit its safety and effectiveness.

Co-encapsulation of paclitaxel and baicalein in nanoemulsions to overcome multidrug resistance via oxidative stress augmentation and P-glycoprotein inhibition.

Multidrug resistance (MDR) is a major obstacle for clinical application of paclitaxel (PTX). Recent studies have suggested that baicalein (BA) might be a potent MDR reversal agent with the ability of P-glycoprotein inhibition and oxidative stress augmentation. Herein, we co-encapsulated PTX and BA in nanoemulsions (PTX/BA NE) for overcoming MDR in breast cancer.

Cellular uptake mechanism and comparative evaluation of antineoplastic effects of paclitaxel-cholesterol lipid emulsion on triple-negative and non-triple-negative breast cancer cell lines.

There is no effective clinical therapy for triple-negative breast cancers (TNBCs), which have high low-density lipoprotein (LDL) requirements and express relatively high levels of LDL receptors (LDLRs) on their membranes. In our previous study, a novel lipid emulsion based on a paclitaxel-cholesterol complex (PTX-CH Emul) was developed, which exhibited improved safety and efficacy for the treatment of TNBC. To date, however, the cellular uptake mechanism and intracellular trafficking of PTX-CH Emul have not been investigated.

Thermal and magnetic dual-responsive liposomes with a cell-penetrating peptide-siRNA conjugate for enhanced and targeted cancer therapy.

Due to the absence of effective in vivo delivery systems, the employment of small interfering RNA (siRNA) in the clinic has been hindered. Here, we describe a novel siRNA targeting system that combines features of biological (cell-permeable peptides, CPPs) and physical (magnetic) siRNA targeting for use in magnetic hyperthermia-triggered release. A siRNA-CPPs conjugate (siRNA-CPPs) was loaded into thermal and magnetic dual-responsive liposomes (TML) (siRNA-CPPs/TML), and in vitro siRNA-CPPs thermosensitive release activity, targeted cellular uptake, gene silencing efficiency, in vivo targeted delivery and in vivo antitumor activity were determined.

Improved safety and efficacy of a lipid emulsion loaded with a paclitaxel-cholesterol complex for the treatment of breast tumors.

The aim of the present study was to develop a lipid emulsion loaded with a paclitaxel-cholesterol complex (PTX-CH Emul) in order to improve the safety and efficacy of paclitaxel (PTX) and evaluate its antitumor activity against commercially available formulation Taxol®. PTX-CH Emul resembling a low density lipoprotein lipid structure, exhibited an ideal particle size, high drug loading capability, high drug encapsulation efficiency and excellent stability. PTX-CH Emul showed superior in vitro anticancer efficacy against triple-negative MDA-MB-231 breast cancer cells when compared with a paclitaxel emulsion (PTX Emul) and Taxol.