Therapeutic delivery最新文献

Aim: Quercetin is a natural dietary compound known for its potential to prevent chronic diseases. However, the translation of this success to humans is hindered due to quercetin's poor oral bioavailability, attributed to its extremely low water solubility and permeability. These challenges affect the oral absorption of quercetin.

Methods: The current work describes a polymer-based platform specifically targeted for the delivery of quercetin to the colon. Quercetin complexes were prepared using co-precipitation. The polymers used are Eudragit® S100/L100/L100-55. Ethanol and polyvinyl alcohol are the solvent and surfactant respectively in the complex formation process.

Results: The formed polymer complexes demonstrate a high loading capacity, reaching approximately 315 μg/mL of quercetin. The complexes obtained were amorphous in the solid state and soluble in buffer with pHs > 5.5. The resulting Quercetin-Eudragit® complexes demonstrate significantly increased aqueous solubility, reaching concentrations > 1 mg/mL. The polymer complexes were more stable for > 30 h in aqueous solutions compared to quercetin. The solubilized Quercetin-Eudragit® formulations demonstrated enhanced reduction in cell viability in colon cancer cells HCT116 and HT29 when compared to quercetin.

Conclusions: In summary, the study demonstrates the successful development of a polymer-quercetin complex with improved loading, solubility, stability, and targeted delivery properties.

Background: This study investigated the in vitro dissolution and in vivo absorption of rifampicin (RIF)-containing 3D-printed tablets using Selective Laser Sintering (SLS) technology.

Methods: In vitro dissolution was assessed in acidic (pH 1.2) and alkaline (pH 6.8) buffer media, while in vivo absorption was evaluated in a New Zealand White rabbit model. Both analytical and bioanalytical methods were rigorously developed and validated using LC-ESI-MS/MS, following ICH Q2 (R1) and FDA guidelines, respectively.

Results: In the acidic medium, 16.22% of RIF was released within the first 2 h, whereas in the alkaline medium, the release increased to 41.75%, indicating a sustained release from the sintered 3D printed tablets. Pharmacokinetic parameters and their corresponding values of C_max (445.38 ± 193.62 ng/mL), T_max (02 ± 0.00 hr), AUC_0-t (841.51 ± 334.13 ng.h/mL), AUC_0-∞ (861.66 ± 340.54 ng.h/mL), K_el (0.61 ± 0.13 h^-1), and t_1/2 (1.18 ± 0.25 hr) were obtained, demonstrating effective RIF absorption in the rabbit. Additionally, an in vitro-in vivo correlation (IVIVC) model was developed, demonstrating a good correlation between in vitro release and in vivo absorption, with R² value of 0.9696.

Conclusion: The results underscore the potential of SLS 3DP technology in advancing the development of RIF-containing 3D printed tablets by sustaining in vitro dissolution following in vivo absorption profiles.

Aims: Synthesis and Characterization of Protein NanoHybrid Systems for the Brain Delivery of Riluzole.

Methods/materials: Fullerene is converted into carboxylated fullerene (CF) and then, prepared RZU-loaded BSA nanoparticles conjugated with CF.

Results: The particle size and zeta potential of RZU-PNH were found to be 210 ± 1.15 nm and -18.5 ± 0.615 mV respectively, and entrapment efficiency and loading efficiency of RZU-PNH were found to be 98.8 ± 0.53% and 11.6 ± 0.43%, respectively. The XRD of the RZU-PNH shows the amorphism behavior and CD revealed that secondary structure of the protein mainly consists of α-helix andβ-sheet. The MTT assay showed 88.60% and 90.84% cell viability in both SH-SY5Yand N2a cell lines at a concentration of 20 μg/ml and also, no significant nasal ciliotoxicity was observed after incubation with RZU-PNH.

Conclusions: Obtained results indicated RZU-PNH formulation to treat amyotrophic lateral sclerosis.

Aims: The goal of the present investigation was to formulate and characterize the Cubosomal in-situ gel of Mirtazapine for intranasal delivery. The cubosomal preparation ensures higher entrapment of drug and delivery through intranasal route improves brain targeting of drug by avoiding the Blood Brain Barrier.

Materials and methods: Cubosomes were prepared by bottom-up approach & Central Composite Design was used for optimization. In-situ thermosensitive gel was formulated by cold method and optimization was done based on gelation temperature and time. The optimized cubosomal formulation was evaluated for various parameters like vesicular size, entrapment efficiency, TEM analysis, in-vitro drug release and ex-vivo permeation study. The cubosomal in-situ gel was evaluated for gelling time, temperature, mucoadhesive and gelling strength.

Results and conclusion: The optimized formulation exhibited 90.33% drug release which confirms that it exhibited superior drug release characteristic as compared to pure drug suspension. The optimized formulation was evaluated for nasal toxicity studies which assure its safety to nasal mucosal membrane. The in-vivo brain biodistribution study showed the Mirtazapine cubosomal in situ gel achieved higher brain concentrations compared to the oral suspension. The cubosomal in-situ gel of Mirtazapine seems to be a promising and safe approach for treatment of depression.

Aims: Diltiazem (DIL), a calcium channel blocker, has demonstrated potential ininhibiting fibrosis-related processes, including TGF-β activation, collagen production, and epithelial-mesenchymal transition, making it a promising candidate for idiopathic pulmonary fibrosis (IPF). This study evaluates the anti-fibrotic efficacy of DIL-loaded chitosan (DIL-CHT) and trimethyl chitosan (DIL-TMC) nanoparticles through molecular and experimental approaches.

Methods: DIL-CHT and DIL-TMC nanoformulations were developed and analyzed particle size, ζ-potential, entrapment efficiency, and in vitro release. Antifibrotic efficacy in bleomycin (BLM)-induced IPF rat model, was tested at subtherapeutic doses (3 mg/kg/day, i.t.) and DIL alone (10 mg/kg/day, p.o.). DFT (B3LYP/6-31 G**) optimization and molecular docking were conducted to assess electronic properties and interactions among CHT, TMC, and DIL.

Results: DIL-TMC and DIL-CHT nanoparticles were 175.6 nm and 267.8 nm, with entrapment efficiencies of 81.72% and 66.0%, respectively; TMC showed a superior 24-hour sustained release. TMC's larger HOMO-LUMO gap (ΔE = -0.260 eV vs. -0.253 eV for CHT) suggests greater stability, supporting its enhanced interaction with DIL. TMC nanoparticles significantly reduced BLM-induced IPF symptoms, i.e. BLM induced increased lung index, hydroxyproline accumulation, oxidative stress in lung tissue, and blood pressure.

Conclusions: These findings indicate the strong therapeutic potential of DIL-TMC for IPF with minimal cardiovascular side effects.

Brain cancer has become an emerging medical disorder that poses a threat to human life due to the uncontrolled growth of cancer cells and their gradual spread to other organs. The most aggressive and life-threatening of the several types of Brain cancer is GBM. Treating GBM is difficult considering drugs are not exposed at the brain's site of action because of BBTB and BBB. Only a few cytotoxic drugs are presently used to treat GBM, including temozolomide, paclitaxel, and doxorubicin, and only temozolomide has enough BBB penetration. In this context, engineered nanoparticles are used to transport chemotherapeutic medications and reduce notable peripheral toxicity on normal cells; for necessary drug dosages. They are investigated as drug carriers to address the problem of drug resistance linked to traditional chemotherapy treatments. Many nanostructures, such as polymeric, lipid-based, and inorganic nanoparticles, have been developed as drug-delivery methods in recent decades. To be therapeutically successful as a GBM therapy, ENP formulations must diffuse through the BBB and efficiently deliver the drugs to the target cells. Various coatings and surface modifications of nanostructures can be tailored with different targeting moieties to facilitate the uptake of drug carriers by malignant cells while safeguarding healthy tissues from damage.

Purpose: Fungal keratitis has a poor prognosis given deep penetration into the corneal stroma. While Rose Bengal photodynamic antimicrobial therapy (RB-PDAT) is a promising adjunct treatment for refractory cases, poor penetration limits its effectiveness. This study explores the penetration depth of alternative photosensitizers to address this issue.

Methods: Thirty-five human corneas were soaked for 30 minutes in 0.0075% solution of Rose Bengal disodium (n = 5), Rose Bengal lactone (n = 5), Erythrosin B disodium (n = 5), Erythrosin B lactone (n = 5), Eosin Y disodium (n = 5), Methylene blue (n = 5), or NaCl (control, n = 5). Confocal microscopy was used to assess penetration depth.

Results: All photosensitizers penetrated greater into the cornea as compared to control. There was no significant difference in penetration between Rose Bengal lactone and Rose Bengal disodium (RB lactone: 106  ± 11 µm vs RB disodium: 99 ± 13 µm, p > 0.05). The penetration depths of the alternative photosensitizers was significantly greater than either Rose Bengal formulation (Erythrosin Blactone: 192 ± 31 µm, Erythrosin B disodium: 163 ± 13 µm, Eosin Y disodium: 249 ± 31 µm, Methylene Blue: 355 ± 151 µm).

Conclusions: Alternative photosensitizers exhibit superior penetration compared to Rose Bengal. However, antimicrobial efficacy and corneal safety require more robust evaluation before clinical use.

The aim of this review is to highlight the role of semisolid systems as vehicles for nanovesicles and nanoparticles. In general, nanotechnology plays a critical role in facilitating the delivery of therapeutic agents to their active sites, and several nanocarrier systems have been explored for the topical administration of active components. The major disadvantage of the prepared nanosystems is their low viscosity, which reduces the time needed for enough absorption and negatively affects their stability and bioavailability. The role of semisolid systems is to overcome this limitation. In conclusion, this review presents an updated summary of recent advances in the use of semisolids as vehicles for various nanosystems through comprehensive scrutiny of the types of semisolids and their advantages and their role in enhancing the absorption of nanoparticles and nanovesicles.

Introduction: Sulphasalazine (Sulf) is a class IV compound with low aqueous solubility and low permeability which limit its therapeutic activity. This work aims to apply choline chloride (CC) and choline hydroxide (CH) as a hydrogen bond acceptor with Sulf for the production of Sulf salt.

Materials and method: New compounds were prepared and characterized by XRD, DSC, and FT-IR. Drug solubility was evaluated in different media including pure water, and buffer pH 1.2, 4.5, and 6.8 were evaluated.

Results: The diffractogram pattern of the Sulf-CH shows a smooth and low-intensity diffraction which may indicate amorphization of the drug molecule. The FT-IR spectra confirm participation of the carboxyl group of Sulf in the formation of hydrogen bonding between Sulf and CH through salt formation which helps to enhance drug solubility. Solubility of Sulf-CH significantly increased up to 10,000-folds in pure water. Sulf-CC caused up to 2-folds enhancement in drug solubility.

Conclusion: The difference in the solubility of Sulf-CC and Sulf-CH may suggest that each of these compounds involve different intermolecular interactions which were also confirmed by FT-IR, XRD, and DSC results. This effect can influence drug bioavailability and enhance its therapeutic efficacy.

Oxygen therapeutics hold great potential as alternatives to red blood cell/whole blood transfusions. The development of hemoglobin-based oxygen carriers began in the 1930s, but, regrettably, none have received FDA approval. This review starts with an overview of red blood cell physiology and then focuses on hemoglobin-based oxygen therapeutics (including modified and encapsulated hemoglobin) as well as red blood cell mimetics, particularly regarding their size and shape. The review also addresses the different approaches to hemoglobin-based oxygen carriers.