Pharmaceutical Development and Technology最新文献

Coenzyme Q10 (CoQ10) is an essential molecule that plays a role in mitochondrial oxidative phosphorylation and acts as a powerful antioxidant. In this study, CoQ10-loaded nanofibers were developed and characterized via electrospinning method. SEM analyses showed that the fiber diameters ranged between 487 and 2163 nm, and that CoQ10 loading did not disrupt the fiber structure but reduced the diameter. It was determined that bead formation was observed only in the F1 formulation due to the low viscosity (73.09 mPas) and conductivity (1.66 mS/cm) values. The F4 formulation, containing Eudragit RL100 and Kollidon 90F, was selected as the final formulation because it exhibited the highest tensile strength (1.49 MPa) and the smallest fiber diameter (1306 nm). In vitro drug release studies demonstrated that the F4 formulation released only 4% of CoQ10 within 24 h, indicating a controlled release profile. The biocompatibility of this formulation was evaluated through a cytotoxicity assay using the SH-SY5Y neuroblastoma cell line. After seven days of treatment, the CoQ10-loaded nanofiber group showed a cell viability of 101.65%. This result indicates that the nanofibers did not exhibit any cytotoxic effect; on the contrary, they demonstrated potential to support cell proliferation. These findings suggest that CoQ10-loaded nanofibers hold promise for biomedical applications.

Etoricoxib (Et) is selective COX-2 inhibitor with several drawbacks after oral administration. Current study focused on formulating targeted Et cubogel for osteoarthritis management. Interaction between formulation factors; (glyceryl-monooleate (GMO) and Poloxamer407 (Px)) concentrations and process parameters (melting/solvent-evaporation preparation methods) was investigated using D-optimal design. Considered levels were 3, 5 and 7% for GMO and 0.5,0.75 and 1% for Px. Effect of selected variables on particle size (PS) and entrapment efficiency (EE) of Et cubosomes was studied using Design Expert software. Optimized formulation was studied for zeta potential, TEM, and Et release. Optimum formula was loaded into gel formulations and subjected to physical characterization and in-vitro Et release. Selected cubogel was evaluated for ex-vivo permeation, and anti-inflammatory activity using carrageenan-induced edema model. Optimum formulation (6.5% GMO,1% Px , melting preparation method) had PS of 58.6 ± 0.51 nm, EE of 96.1 ± 1.5%, zeta potential of -26.6 ± 0.66 mV and cubic structure as indicated by TEM. Formulated cubogels had acceptable physical properties with sustained release depending on gelling agent type and concentration. Ex-vivo permeation confirmed higher permeability for Et cubogel than Etgel. Anti-inflammatory study confirmed enhanced (p < 0.05) anti-inflammatory activity of Et cubogel as compared to Et gel. Hence, the present study presents Et cubgel formulation as anti-inflammatory remedy.

In this study, the efficacy of a Nanogel Composite was evaluated and compared to the conventional drug carmustine (BCNU) through ex vivo and in vivo studies using New Zealand White rabbits. The Nanogel Composite is a thermosensitive, electro-responsive, and mucoadhesive gel containing BCNU-loaded paramagnetic nanoparticles known as Nano-co-Plex (NCP). Following intranasal administration, electrical stimulation (ES) was applied to the rabbit's nasal cavity, initiating the release of BCNU-NCP. Subsequently, a magnetic headband placed on the rabbit's head rapidly attracted the released nanoparticles toward the brain. The in vivo results showed high amount of BCNU in cerebrospinal fluid (CSF) and the brain of the rabbit for Nanogel Composite compared to the conventional drug with BCNU concentration values in the CSF, brain and plasma being 0.2571 µg/mL, 0.199 µg/g and 0.0078 µg/mL, respectively, after 30 min of administration with the application of ES and MF; and 0.0087 µg/mL, 0.0076 µg/g and 0.0078 µg/mL without the application. The system enabled a pulsatile 'on-off' release profile, improving drug localization in the brain while minimizing systemic exposure. The applied ES and MF conditions (5 V and 0.4 Tesla) were found to be safe and well-tolerated, indicating the potential of this dual-stimuli-responsive platform for effective, non-invasive, and controlled nose-to-brain drug delivery.

Diabetes mellitus (DM) is among the most prevalent illnesses in the world. DM and its complications lead to high mortality rates. The negative effects of traditional diabetic therapies, such as insulin and metformin, include weight gain, hypoglycemia, and gastrointestinal problems. In addition to the limited compliance of patients using insulin injections as a treatment for diabetes, these injections cause pain, discomfort, and local infections. This review illustrates the application of nanotechnology (NT) in the treatment of diabetes, especially since it has become an important area of research over the past several decades owing to its application in various sectors, such as biomedicine, cosmetics, and food. This review focuses on the different uses of nanoparticles (NPs), for example zinc oxide (ZnO-NPs), manganese oxide (MnO-NPs), magnesium oxide (MgO-NPs), and selenium (Se-NPs), and their role in controlling diabetes. The application of ZnO-, MnO-, MgO-, and Se-NPs allows the administration of relatively small but more effective doses in the treatment of DM to reduce side effects and increase therapeutic effects by decreasing oxidative stress and increasing antioxidants, insulin sensitivity, and glucose consumption. NT can also be used to improve drug formulations by enhancing drug solubility and altering pharmacokinetics, to prolong drug release and bioavailability.

Persistent postoperative pain is commonly occurred after surgical procedures, while over half of patients suffer from poorly controlled pain, due to the limited therapeutic period of commercial drugs and suboptimal drug delivery strategy. Herein, an injectable sustained-release gel was developed by a combination of ropivacaine (a local anesthetic) and lornoxicam (a nonsteroidal anti-inflammatory drug), which formulated by poly(ortho esters) (POE) to regulate the sustained-release behavior. POE with low molecular weight was synthesized and employed to prepare the ropivacaine and lornoxicam sustained-release gel (RL-SRG) with the rheological characteristics of temperature-sensitivity. In vitro release studies demonstrated that RL-SRG exhibited sustained release for 72 h. The RL-SRG was stable for 3 months at 40 ± 2 °C and a relative humidity of 75 ± 5%. In vivo pharmacokinetic studies in rats indicated that RL-SRG maintained the plasma concentrations of ropivacaine and lornoxicam for 3 days. Compared to commercial products, RL-SRG prolonged the time of peak concentration (T_max), mean residence time (MRT), and elimination half life (t_1/2), as well as possessed similar the area under the plasma concentration-time curve (AUC_0-t). Therefore, RL-SRG has been validated as a novel sustained release system to the application for the long-term treatment of postoperative pain.

Nimodipine (NMP), a poorly water-soluble small-molecule agent, demonstrates notable therapeutic limitations in addressing cerebral vasospasm secondary to subarachnoid hemorrhage (SAH). Owing to its inherent physicochemical properties characterized by low oral bioavailability, rapid elimination half-life, and extensive first-pass metabolism, conventional formulations necessitate frequent dosing regimens to sustain therapeutic plasma concentrations. These pharmacological challenges collectively result in suboptimal patient adherence, marked plasma concentration fluctuations, and recurrent vascular irritation. To overcome these pharmacological constraints, this investigation engineered a novel drug-loaded microsphere system utilizing poly(5-(p-carboxyphenoxy) valeric anhydride (Poly(CPV)) as a biodegradable matrix material. The sustained-release microspheres were fabricated via microfluidic technology to systematically address the clinical challenges associated with frequent dosing regimens. The optimized microspheres exhibited a drug loading capacity of 5.59%, an encapsulation efficiency of 70.22%, and a uniform particle size distribution (43.98 ± 4.29 μm). In vitro release studies demonstrated sustained drug release over 14 days. Pharmacokinetic evaluation in rats revealed that the NMP-loaded microspheres maintained relative stable plasma drug concentrations for approximately 10 days. Biocompatibility assessments, including histocompatibility tests and in vitro cytotoxicity assays, confirmed the excellent biocompatibility of the Poly(CPV) microsphere. These findings suggest that Poly(CPV)-based microspheres prepared by microfluidics represent a promising drug delivery platform for poorly soluble small-molecule pharmaceuticals, offering controlled release characteristics and improved therapeutic outcomes.

The objective was to prepare a mucoadhesive buccal film containing amphiphilic dendrimer micelles nanoparticles (APD micelles NPs) loaded with insulin. The APD micelles NPs were synthesized by a series of chemical reactions followed by self-assembly. Insulin loading was done by mixing insulin with APD micelles solution. A mucoadhesive buccal film was prepared using solvent casting method. Stability of the buccal film after 3 months of storage in a refrigerator was investigated in terms of viscosity, drug loading, FTIR, in vitro drug release and morphology. The APD micelles NPs had good encapsulation efficiency and good loading capacity. FTIR results showed no interaction with the drug. In vitro release of insulin was glucose sensitive, increasing with time and with glucose levels and sustained for 8-10 h. The Loaded buccal film showed good physical appearance, excellent folding endurance, good mucoadhesive and tensile strength, neutral surface pH, acceptable thickness and weight. Insulin release from buccal film was not affected by the extra barrier. The stability study indicated that the film did not show any changes. In conclusion, APD micelles NPs were able to control insulin release according to glucose levels. The buccal film is expected to enhance the bioavailability of insulin compared to oral administration.

Background: Polycystic ovarian syndrome (PCOS) is the most prevalent endocrine disorder in women of reproductive age, leading to issues such as androgen excess, insulin resistance, obesity, and menstrual irregularities. Quercetin (QCT), a plant polyphenol, is effective in treating PCOS by regulating steroidogenic activity and helping to correct hormonal imbalances.

Methods: In this research, a hydrogel formulation containing QCT-loaded chitosan (CS) and polyvinyl alcohol (PVA) was developed for the treatment of polycystic ovary syndrome (PCOS). The hydrogel was evaluated for various characteristics including pH (ranging from 4.3 to 5.3), spreadability (11.4 to 36.4 g cm/s), swelling index, viscosity, and in vitro drug release, revealing suitable parameters for its application. The release behavior indicated a non-Fickian diffusion mechanism, with a diffusional exponent of 'n ≥ 0.5,' demonstrating effective in vitro QCT delivery. Characterization techniques such as FT-IR, SEM, and DSC were employed to confirm the properties of the hydrogel. Subsequent in vivo studies on PCOS rat models showed significant results, including the recruitment and proliferation of normal ovarian follicles and the normalization of hormone levels, supporting the hydrogel's potential for effective PCOS therapy.

Conclusion: The study indicates that QCT-hydrogel is more effective than commercial preparations and represents a safe, natural topical therapy for PCOS.

Age-related macular degeneration (AMD), first identified in the 1840s, is now considered the leading cause of visual impairment in elderly people in Western societies. This condition affects the macula, a region rich with photoreceptors essential for detailed visual resolution and colour vision. Advanced AMD can be either atrophic (dry) or exudative (wet), and both forms may coexist. Exudative AMD is characterised by choroidal neovascularisation, where abnormal blood vessels invade the retina and the retinal pigment epithelium (RPE), leading to fluid accumulation in sub- and intra-retinal compartments and photoreceptor dysfunction. In contrast, atrophic AMD involves the gradual degeneration of the RPE and outer retinal layers. Current treatments, such as anti-vascular endothelial growth factor (anti-VEGF) therapies for exudative AMD, can slow or halt disease progression but do not offer a cure. Over the past decade, extensive research programs have focused on various pathogenetic mechanisms of AMD, including oxidative stress, inflammation, and complement pathway dysregulation. This review aims to highlight current theories for developing new treatments, compile recent discoveries and insights into AMD pathogenesis and disease progression, and place special emphasis on therapeutic approaches that have reached clinical trials, evaluating their findings wherever possible.

Strontium (Sr) is a bone-seeking element characterized by its dual function of stimulating bone growth and preventing bone resorption. On the other hand, alginates (Alg) have distinct physicochemical characteristics from other natural polysaccharides because of their ability to encapsulate proteins and drugs. This work aimed to prepare novel hybrid inorganic/organic strontium alginate (Sr-Alg) nanoparticles for use as a targeting ligand in bone regeneration. These hybrid nanoparticles were prepared by a simple precipitation technique and different formulation variables were studied. The optimized formulation showed the most promising particle size (133.80 ± 2.40 nm) and zeta potential (-31.5 ± 1.45 mV). Moreover, the selected formulation was subjected to characterization using FTIR and X-ray diffraction to confirm the formation of the hybrid structure. The selected formulation was subjected to an in vivo study and compared with calcium alginate nanoparticles. Mice treated with Sr-containing formulation showed significant improvement in Ca/P and Ca + Sr/P ratios reached 1.799 ± 0.01 and 1.89 ± 0.01, respectively. An in vivo toxicity study was also assessed based on biochemical assays and histological examination of liver and kidney tissues and confirmed that non-significant nephrotoxic or hepatotoxic effects were demonstrated in the treated groups. Therefore, Sr-Alg could be considered a promising targeted ligand for bone regeneration with enhanced safety and efficacy.