Pharmaceutical Development and Technology最新文献

3D printing is emerging as a transformative technology in pharmaceutical manufacturing, enabling personalized medicine and innovative dosage forms. It allows precise control over drug release and dosage customization, addressing individual patient needs. Various 3D printing techniques, including fused deposition modeling (FDM), are being explored for pharmaceutical applications. The choice of polymers and their rheological properties is crucial for successful extrusion-based printing. While 3D printing accelerates drug development, challenges remain regarding quality control. Quality-by-design (QbD) approaches are essential to ensure safe and effective pharmaceutical products. This study highlights the role of critical process parameters (CPPs), such as infill density and printing speed, in producing poly(lactic acid)-based intravaginal rings. The effects of CPPs on critical quality attributes (CQAs), such as ring dimensions, weight, and swelling degree, were examined. Printing speed (25-100 mm/s) and infill density (0-20%) significantly affected weight and dimensions, with average weights ranging from 0.537 g to 0.629 g. Internal dimensions varied between 9.73 mm and 9.81 mm, while external dimensions ranged from 19.43 mm to 19.69 mm. Rings printed at the lowest speed and highest infill density showed the greatest swelling (2.47%). These findings confirm FDM as a viable method for producing cost-effective, patient-specific intravaginal rings with reproducible results.

This study aims to develop an alternative and effective drug delivery system through inhalation therapy to address the limitations of polymyxin B (PMB) intravenous treatment for pneumonia. PMB dry powder inhalers (DPIs) were prepared and characterized. The in vitro lung deposition and antibacterial efficacy were also assessed. To compare the systemic exposure following changes in administration routes, blood concentration measurements were conducted for different routes of administration spherical PMB particles, measuring 3 microns in diameter, achieved the highest fine particle fraction (FPF) of 53%. When particles transition from regular shapes to irregular blocks, a decrease of 1 micron in particle size resulted in an approximate 20% increase in FPF. Moreover, the FPF of PMB particles combined with smooth-surfaced lactose was approximately 10% less than that of PMB particles combined with rough-surfaced mannitol. The bioavailability of PMB DPI reached a peak of 77.46% within 10 min. In a murine model of acute lung infection, treatment with PMB DPI significantly reduced the bacterial load in lung tissues compared to the control group with intravenous PMB administration. In summary, particles with reduced size and increased sphericity displayed a greater FPF led to enhanced therapeutic efficacy and safety.

In order to enhance the therapeutic value of curcumin in liver cancer treatment, glycyrrhetinic acid-modified pH-sensitive curcumin liposomes (GA-pH-Lip@Cur) was developed.GA-pH-Lip@Cur was prepared using a thin film dispersion ultrasonication method, and the optimal formulation process was selected through single-factor experiments and a Box-Behnken design-response surface methodology. The liposomes were evaluated for their morphological appearance, particle size, in vitro release at different pH levels, and biocompatibility. The anti-tumor effect of GA-pH-Lip@Cur was assessed using cell viability assays (CCK-8). The in vivo hepatic targeting and anti-liver tumor efficacy of GA-pH-Lip@Cur were evaluated through pharmacokinetic and pharmacological experiments.The results indicated that optimized GA-pH-Lip@Cur exhibited uniform particle size distribution, good stability, pH-sensitive in vitro release with sustained behavior. Compared to conventional liposomes, GA-pH-Lip@Cur showed prolonged average retention time in vivo and significantly increased curcumin distribution in liver tissues, indicating excellent liver targeting. Both in vitro and in vivo evaluations demonstrated the effectiveness of GA-pH-Lip@Cur in inhibiting liver cancer cell proliferation and suppressing liver tumor growth in tumor-bearing mice. In conclusion, GA-pH-Lip@Cur, by leveraging the acidic tumor microenvironment and overexpression of glycyrrhetinic acid receptors in liver cells, encapsulates curcumin to improve its bioavailability, and target its delivery to the liver tumor sites.

The exploration of novel carriers for cancer treatments is on the rise, as drugs are often hindered by ineffective delivery. In the present study, Mesoporous silica nano scaffolds were developed by a novel heat assisted hydrolysis (HAH) technique, and were functionalized using PLGA. These carriers were further loaded with nanosized Gefitinib (GTB). The surface properties of MSNs (GTB-PEG-PLGA-MSN) were enhanced using 1-oleoyl-2-hydroxy-sn-glycero-3-phosphocholine (SPC3). The MSNs were characterized for pore volume, particle size, zeta potential (ZP), surface area, entrapment efficiency (%EE), and drug content. The in vitro drug release kinetics, cytotoxicity analysis, and in vivo biodistribution studies were performed in optimized MSN using Albino Wistar rats. The result shows an increase in surface area, pore volume, %EE, and drug loading in MSN. In vitro cytotoxicity of optimized F5-GTB-PEG-PLGA-SPC3-MSN demonstrated a higher antitumor activity (43.84 ± 0.63%, p < 0.05) in comparison to free drug. A higher GTB was detected in the liver (29,415 ± 126 ng) indicating significant biodistribution (p > 0.05). The in vitro studies in the MCF-7 cell line signify an increase in cell viability demonstrating its efficacy in breast cancer. Optimized F5-GTB-PEG-PLGA-SPC3-MSN offers improved cellular uptake, biodistribution, and higher antitumor suppression with less toxicity. To conclude, the HAH technique produced stable MSNs, and PLGA-SPC3 functionalized MSN nano scaffolds could be an ideal carrier for cancer drug delivery.

The aim of this study was to develop and evaluate an extended-release (ER) push-pull osmotic pump (PPOP) tablet for phencynonate HCl (PCN), which could release the drug at zero-order profile for a duration of 24 h. The core tablets were designed as bi-layered, primarily composed of sodium chloride and polyethylene oxide (PEO). The central composite design (CCD) within a response surface methodology (RSM) was used to optimize the formulation. An optimized PCN-PPOP tablet formulation was achieved with the following values for key factors: 10 mg NaCl, 70 mg PEO, and 13.56% coating membrane weight gain. It revealed that this formulation could release PCN in vitro at a zero-order manner for 18 h. The in vivo release property of the PCN-PPOP tablet was assessed and contrasted with that of immediate-release (IR) tablet following a single oral administration to beagle dogs. The pharmacokinetic data indicated that the PPOP tablet achieved a sustained in vivo release of PCN, as evidenced by a longer T_max (7.17 ± 1.83 h) and mean residence time (11.57 ± 1.12 h). This work demonstrated that PCN-PPOP tablet could be designed for oral administration to provide a long-term pharmacological intervention for motion sickness.

Intravitreous long-acting drug delivery system offers an excellent alternative to multiple injections for the treatment of noninfectious uveitis (NIU). However, the adverse effects of non-biodegradable intravitreal implants of fluocinolone acetonide (FA), such as postoperative hypotony and secondary injury during removal of the implant matrix, are frequent occurrence to affect patient's compliance. Herein, biodegradable poly (lactic-co-glycolic acid) (PLGA)-based microspheres (MS) containing fluocinolone acetonide (FA@MS) were prepared using an optimized electrospray technology with a voltage of 10.07 kV and the receiving distance of 9.87 cm. The obtained FA@MS with the average particle size of 2.25 μm possessed the high encapsulation efficiency (94.85%) and drug content (9.48%). In vitro release demonstrated that FA@MS exhibited sustained release for 30 days, and the release characteristic of FA@MS conformed to the Weibull model. In vivo study in a rabbit NIU model indicated that FA@MS continuously released the drug for at least 28 days in vitreum and progressively decreased inflammation of NIU. Furthermore, the intraocular pressure of rabbits treated with blank MS and FA@MS remained the normal level for 28 days, which demonstrated the favorable biosafety of FA@MS. In conclusion, long-acting release of FA@MS provides a promising formulation for NIU treatment.HIGHLIGHTSA biodegradable FA@MS was prepared using the modified electrospray technology for intravitreal administration.FA@MS exhibited the sustained release characteristics for 30 days in the medium of PBS (pH 7.4) with 0.2% Tween 80.The pharmacodynamics indicated that FA@MS could be continuously released for at least 28 days in vitreum to treat NIU.

Cinacalcet hydrochloride (HCl), a calcium-sensing receptor agonist used to treat hyperparathyroidism, suffers from poor solubility, reducing its bioavailability. Recently, cinacalcet HCl has been probed for repurposing as antibacterial agent. This work investigates cinacalcet HCl's potential as an antibacterial agent and provides a formulation to improve the drug dissolution. Solid dispersion formulations using Poloxamer 407, with and without Soluplus^®, were prepared via solvent evaporation and hot melt congealing methods. The resulting formulations were analyzed using differential scanning calorimetry, FTIR spectroscopy, X-ray powder diffraction, and dissolution studies. These formulations significantly enhanced cinacalcet HCl dissolution compared to the unprocessed form, achieving up to a 15-fold increase in Q5 (percent of cinacalcet HCl dissolved after 5 min). The dissolution efficiency rose from 28% for the pure drug to 94.8 and 87.8% for formulations F6 and F7, respectively. Microbiological evaluations confirmed the antibacterial effect of cinacalcet HCl, which was notably increased in the Poloxamer 407 and Soluplus^® hybrid formulation (F7) with a MIC of 64-128 µg/ml. Antibiofilm activity was also observed, with qRT-PCR indicating downregulation of biofilm genes (icaA, icaD, and fnbA). This study introduces a cinacalcet HCl formulation prepared using a scalable, green approach, demonstrating significant potential for antimicrobial applications.

Tear trough deformity (TTD) is a significant cosmetic concern, with current treatments relying primarily on invasive injectable fillers, which are costly and carry risks of complications. Despite the widespread use of hyaluronic acid (HA) in cosmetic applications, its poor dermal permeation has limited the development of effective topical fillers for TTD. This study aim to develop and evaluate a novel hyaluronic acid nanogel (nanofiller, NF) as a non-invasive topical filler for TTD. The hyaluronic acid NF was formulated and characterized for size, zeta potential, and skin permeation using the Franz diffusion method. The nanofiller demonstrated a particle size of 213.28 ± 4.15 nm and a zeta potential of -22.1 ± 1.07 mV, with a tenfold superior permeation compared to conventional HA gel. Thirty adult female patients aged 21-50 years with TTD were enrolled in a clinical trial and randomly assigned to receive either the NF or a conventional HA gel (control). Participants were randomly assigned to receive either the NF or a conventional HA gel (control). Clinical evaluation included subjective assessments and objective photomorphometric measurements of TTD parameters such as skin roughness (fine lines), indentation index, mean density, and percentage of the affected area. The NF group showed a significant improvement in TTD parameters, including up to a 40-fold reduction in skin roughness and indentation index, with 100% patient satisfaction and no adverse effects, compared to the control group. "To conclude; this study demonstrates the efficacy and safety of the HA nanofiller as the first effective topical treatment for TTD, offering a non-invasive alternative to injectable fillers.

In this paper, the pH-sensitive targeting functional material NGR-poly(2-ethyl-2-oxazoline)-cholesteryl methyl carbonate (NGR-PEtOz-CHMC, NPC) modified quercetin (QUE) liposomes (NPC-QUE-L) was constructed. The structure of NPC was confirmed by infrared spectroscopy (IR) and nuclear magnetic resonance hydrogen spectrum (¹H-NMR). Pharmacokinetic results showed that the accumulation of QUE in plasma of the NPC-QUE-L group was 1.28 times and 2.43 times that of the QUE Solution and QUE-L groups, respectively. The release amount of NPC-QUE-L in an acidic environment was significantly higher than in physiological pH value. The order of the tumor cell inhibition rate in different pH environments was NPC-QUE-L > PC-QUE-L > QUE-L. In addition, the cellular uptake of NPC-modified liposomes was higher than that of PC-modified and unmodified liposomes, indicating that NPC had good pH-sensitivity and targeting. In the triple-negative breast cancer (TNBC) model, the relative tumor proliferation rate of NPC-QUE-L is about 73%, which is better than that of the QUE solution group. Western blot results show that NPC-QUE-L can effectively reduce the expression of α-smooth actin and transforming growth factor-β1 in tumor tissues, and improve the degree of tumor fibrosis. In this study, NPC could endow QUE liposomes with good stability, pH-sensitivity, and targeting, which provides a reference for improving the solubility and targeting of poorly soluble natural drug components.

Zinc oxide NPs (ZnO NPs) are notable in nanomedicine for their exceptional physicochemical and biological properties. This study synthesizes and characterizes beta-carotene-coated ZnO NPs (BT-ZnO NPs) for potential anti-cancer and antimicrobial applications, demonstrating significant efficacy against dental pathogens and oral cancer cells. Scanning Electron Microscopy, EDAX, UV, FTIR, XRD, and Zeta potential analysis of prepared BT-ZnO NPs revealed uniform flower-like crystalline structures with intricate morphology and an average particle size of 38.06 nm. FTIR spectra identified various functional groups, suggesting a complex organic compound coated with ZnO NPs. Zeta potential measurements showed pH-dependent surface charge variations, which are crucial for understanding colloidal stability. The antimicrobial activity was potent against dental pathogens, with minimum inhibitory concentration (MIC) values of 50 µg/mL highlighting significant inhibition. Molecular docking studies demonstrated strong binding affinities of BT to key receptor proteins of dental pathogens. BT-ZnO NPs exhibited notable antioxidant activity of 68%, comparable to ascorbic acid, and significant anti-inflammatory effects of 75.1% at 100 µg/mL. Cytotoxicity assays indicated a concentration-dependent suppression of KB cell proliferation, decreasing cell viability to 37.19%, and gene expression studies showed elevated P53 expression, suggesting a strong apoptotic response. These multifaceted properties underscore the potential of BT-ZnO NPs as an integrated therapeutic approach for dental healthcare and oncology.