Pharmaceutical Development and Technology最新文献

Baicalin is a flavonoid glycoside with substantial biological activity and pharmacological effects, primarily extracted from Scutellaria baicalensis Georgi. However, its clinical implementation has been impeded by suboptimal aqueous solubility and unfavorable bioavailability. This study employed a supercritical anti-solvent (SAS) process to prepare amorphous solid dispersions of baicalin, aiming to enhance its dissolution and bioavailability. The effects of supercritical temperature, supercritical pressure, and CO₂ flow rate on encapsulation were thoroughly investigated using the Box-Behnken Design (BBD) response surface methodology. SEM, FTIR, DSC, and XRD analyses confirmed that the baicalin solid dispersion prepared via the SAS method was in an amorphous state. In vitro dissolution tests indicated that the solubility of baicalin in the solid dispersion was 9.4 times (pH = 6.8) greater than that of the raw baicalin particles. Furthermore, rat experiments revealed that the bioavailability of baicalin in the solid dispersions was 1.8 times higher than that in traditional particles. Notably, BASD exhibited strong inhibitory effects on the growth of Bacillus subtilis and Escherichia coli. Consequently, a solid dispersion of baicalin was successfully prepared using the BBD-optimized SAS process, significantly enhancing the performance of baicalin.

In the present study, three kinds of curcuminoids (CS)-loaded micelles (CS-NPGS) were prepared by the solid dispersion method using novel Nitogenin polyethylene glycol succinate-1000 (NPGS-1000) to enhance the solubility and bioavailability. The micelles were characterized using a particle size analyzer, a crystallography analyzer, and Fourier transform infrared spectroscopy (FT-IR). The morphology was screened using a scanning electron microscope. In vitro release profiles of curcumin from CS-NPGS showed a sustained release without rapid burst. Treating triple negative MDA-MB-231 cell lines with all micelles remarkably exhibited dose-dependent toxicity and inhibited the cell proliferation. Epifluorescence was used to evaluate the morphology of the treated cells by using various stains. The IC50 values of the curcumin-loaded micelles against triple negative MDA-MB-231 cells were 10.85, 5.43, and 5.43 μg/mL for CS-NPGS-1, CS-NPGS-2, and CS-NPGS-3, respectively, lower than the one of free curcumin (21.7 μg/mL). An in vivo rat oral pharmacokinetic study showed 13.25x, 16.43x, and 18.51x increases in Cmax for CS-NPGS-1, CS-NPGS-2, and CS-NPGS-3 compared to curcuminoid powder, respectively. The relative bioavailability of CS-NPGS-1, CS-NPGS-2, and CS-NPGS-3 was 155.21%, 504.82%, and 687.83% compared to CS, respectively. The aqueous solubility of encapsulated CS-NPGS micelles is considerably improved, allowing for more localized drug delivery and a superior treatment alternative for residual cancer tumors.

Acacetin, a natural flavonoid with high-melting-point (> 200 °C) and poorly aqueous solubility, presents significant challenges in oral bioavailability due to its low dissolution rate. To address this limitation, acacetin-loaded amorphous solid dispersion (ASD) were developed via a quality-by-design (QbD) framework and manufactured using solvent-free hot-melt extrusion (HME). The formulation incorporated Soluplus as the polymeric matrix and d-a-tocopherol polyethylene glycol succinate (TPGS) as multifunctional plasticizer. The amorphization of acacetin was confirmed by differential scanning calorimetry (DSC) and Powder X-ray diffraction (PXRD). The optimized ternary system Aca-Soluplus-TPGS (2:6:2, w/w/w) achieved solubility 32.5 ± 11.5 μg/mL in simulated gastric fluid (SGF, pH 1.2), 180.5 ± 1.5 μg/mL in simulated intestinal fluid (SIF, pH 6.8), and 211.5 ± 6.3 μg/mL in water, respectively, 2203- to 3142-fold improvements over Aca. In single-pass intestinal perfusion (SPIP) studies, the optimized formulation exhibited 23.7 μg/cm² intestinal absorption per unit area, a 1.2-fold increase compared to Aca. The pharmacokinetic of Aca-Soluplus (2:8), Aca-Soluplus-TPGS (2:6:2), and Aca-Soluplus-TPGS (2:2:6) showed relative bioavailability of 698.0%, 725.2%, and 1456.3%, respectively, compared to Aca. Stability testing (40 °C/75% RH, 6 months) confirmed no recrystallization, indicating the robustness of the HME-based ASD strategy. These findings highlight HME as a scalable, solvent-free and continuous approach to enhance the biopharmaceutical performance of high-melting-point compound Aca.

The present paper provides a detailed overview of surfactants' function in HIV/AIDS therapy, with a focus on medication administration, direct antiviral mechanisms, and microbicide formulations. The use of surfactant-based nanotechnology into antiretroviral therapy has resulted in the development of liposomes, polymeric micelles, nanoemulsions, and surfactant-modified biomaterials that provide controlled release and increased bioavailability of antiretrovirals. Furthermore, many surfactants have inherent antiviral activity, which disrupts the viral lipid envelope, inhibits viral replication, and prevents HIV from entering host cells. The paper also explores the potential of surfactant-based biosensors for HIV diagnostics, emphasizing their role in improving sensitivity and selectivity and recent progress in formulation design using surfactants such as sodium lauryl sulfate, poloxamers, and biosurfactants, emphasizing their safety, biocompatibility, and clinical potential. Key challenges including scalability, environmental impact, and user acceptability are discussed alongside emerging AI-driven approaches for personalized nanomedicine. Surfactant toxicity and limited biocompatibility remain key barriers. Developing safer, more effective surfactants is essential for future clinical progress.

Aim/background: Ensuring smooth and consistent vial flow on pharmaceutical filling line conveyors is essential for maintaining sterility, reducing downtime, and avoiding costly disruptions. However, irregular vial movement such as spacing gaps, clustering, and vial flipping is often seen, leading to filling delays, broken glass, machine stoppages, and extended batch times. Existing systems lack the ability to detect such irregularities in real time and provide actionable alerts.

Materials and methods: A lightweight, AI-guided framework was developed for detecting vial flow irregularities and classifying bottleneck risks using computer vision. A high-speed camera positioned above the conveyor captured video frames processed by YOLOv8 for real-time object detection. OpenCV was used to extract vial positions and calculate flow metrics (average spacing, standard deviation, inter-vial gap thresholds). A rule-based classification system assigned bottleneck risk levels: low, medium, or high. Operational conveyor footage from a pharmaceutical filling line was analyzed; to protect confidentiality, frames were de-identified and re-rendered as schematic visualizations that preserve vial geometry and spacing statistics.

Results: Across 15 operational frames, the classifier achieved accuracy 93.3%, F1-macro 95.21%. On throughput, the end-to-end pipeline processed frames at ∼18 FPS on CPU and ∼25 FPS on Jetson Nano. Detector evaluation yielded mAP@0.5 = 100.00%, mAP@[0.5:0.95] = 70.09%, precision = 98.65%, recall = 100.00%, F1 = 99.32% at confidence 0.50.

Conclusion: This scalable, non-invasive solution can be integrated into existing pharmaceutical lines to improve operational efficiency and product integrity. The rule-based approach offers interpretability, making it suitable for GMP-regulated environments. Across the operational validation set, the risk classifier achieved macro average precision 95.24%, recall 95.83%, and F1 95.21% .

Carbon-based nanoparticles (CNPs) have attracted significant attention as photosensitizers for photodynamic therapy (PDT) due to their biocompatibility, facile synthesis, and ability to generate reactive oxygen species (ROS). In this study, green-synthesized gallic acid CNPs (GACNPs) were optimized and characterized for their physicochemical properties and biomedical potential. GACNPs exhibited no cytotoxicity to normal cells at concentrations up to 250 µg/mL, demonstrating excellent biocompatibility. Under LED light irradiation (350-700 nm, 0.124 W/cm², 10 min), GACNPs efficiently generated ROS, as assessed by photodynamic activity and intracellular ROS detection, confirming their photosensitizing function. The anticancer efficacy of GACNPs was evaluated in HeLa and MDA-MB-231 cell lines, revealing IC₅₀ values of 2.92 ± 0.14 µg/mL (exposure) versus 3.74 ± 0.22 µg/mL (non-exposure) for HeLa and 2.62 ± 0.24 µg/mL (exposure) versus 4.14 ± 0.19 µg/mL (non-exposure) for MDA-MB-231 cells, indicating significantly enhanced cytotoxicity upon light exposure. Furthermore, both cell lines showed that GACNPs significantly enhanced the anticancer effect upon exposure compared to the GA solution. Apoptosis assays showed 64% cell death after exposure, compared to 47% without exposure, in HeLa cells, and 93% cell death after exposure, compared to 74% in MDA-MB-231 cells. These findings demonstrate that GACNPs are promising nano-photosensitizers for PDT-based cancer therapy, combining low cytotoxicity with high ROS-mediated anticancer efficacy.

Lapatinib ditosylate (LD) is a chemotherapeutic agent that belongs to Class II of the Biopharmaceutical Classification System. The objective of this work was to enhance oral bioavailability of LD by developing a nanoparticle solid dispersion. Lapatinib ditosylate nanoparticles (LDNP) were prepared by a combination of precipitation followed by high pressure homogenization. The optimized LDNP formulation, containing LD, hydroxypropyl methyl cellulose acetate succinate, Brij-35, and sodium lauryl sulfate in the ratio of 1:4:0.5:0.2, was found to provide an average particle size of 103 ± 4.6 nm after freeze drying. Scanning electron microscopy and solid-state characterization revealed rounded particles in an amorphous state. Nanonization significantly (p < 0.05) increased dissolution rate (90 ± 4.6% within 30 min) compared with the physical mixture (29 ± 1.3% in 30 min). Pharmacokinetic evaluations performed in Wistar rats showed 1.3- and 1.4-fold increase in C_max and AUC_total after LDNP administration compared with commercial formulation. LDNP demonstrated similar growth inhibition in oral carcinoma MOC2 and FaDu cells as that of LD solution. LDNP showed complete remission of xenografted oral cancer in a C57BL/6 mouse model after seven doses of 100 mg/kg LDNP. The LDNP formulation can be developed to enhance the oral bioavailability of LD for effective oral cancer treatment.

Skin cancer's rising global incidence and the significant limitations of conventional therapies, such as systemic toxicity and drug resistance, necessitate the development of more effective and personalised treatment strategies. The emergence of MN integrated, stimuli-responsive platforms as an advanced therapeutic approach for skin cancer offers to bypass the skin's primary barrier, the stratum corneum, enabling targeted, localised delivery of therapeutic agents. By incorporating 'smart' materials, these platforms can release their payload in response to specific endogenous stimuli within the tumour microenvironment (e.g. pH, enzymes, redox potential) or externally applied triggers (e.g. Light, Temperature, ultrasound). This allows for on-demand, controlled release, enhancing therapeutic efficacy while minimising systemic side effects. This review focuses on the synergistic integration of these technologies, analysing how they enable potent combination therapies. Preclinical studies have demonstrated the potent synergistic effects of these platforms, particularly in combining chemo, photothermal (PT), and immunotherapies, achieving high tumour inhibition rates in animal models. However, translation to clinical settings faces challenges, including drug loading capacity, mechanical reliability, scalable manufacturing, and complex regulatory pathways. Current clinical trials are cautiously validating simpler, single-agent MN systems for non-melanoma skin cancers. This review highlights that while significant hurdles remain, the integration of MNs with stimuli-responsive systems represents a powerful strategy, with future developments in theranostics and closed-loop systems poised to revolutionise personalised skin cancer therapy. Future developments in theranostics, wearable biosensors, and closed-loop feedback systems are poised to overcome current limitations, offering a forward-looking perspective on cost-effective, patient-centric treatments that can adapt to the evolving biology of the disease.

Redox-responsive nanocarriers exploit the unique intracellular redox environment to enable targeted and controlled release of therapeutic agents. The present study comprises the fabrication of Palbociclib-bearing Bovine serum albumin-based redox-responsive nanoparticles (RR-PAL-NPs) through self-crosslinking using the desolvation technique. The optimisation of the formulation was achieved using the Box-Behnken design of experiment. The RR-PAL-NPs particle size, PDI, zeta potential, and percentage entrapment efficiency are 195.56 ± 9.99 nm, 0.22 ± 0.01, 3.9 ± 0.12 mV, and 91.23 ± 3.8%, respectively. In the presence of 10 mM glutathione, at pH of 5.5 and 7.4, nearly all the PAL was released from RR-PAL-NPs, making a release of 88.98 ± 3.00 and 82.41 ± 3.9%, respectively. Furthermore, dilution study, turbidimetric analysis, UV and spectrofluorescence analysis, circular dichroism, stability study, pH titration, and hemocompatibility study were also performed, which deemed the formulation satisfactory. RR-PAL-NPs depicted an exceptional in vitro cytotoxic and apoptotic profile. An outstanding mitochondrial depolarisation, ROS generation, inhibition of colony formation, wound healing, and glutathione depletion were seen. In the 3D mammosphere study, it caused a 3.57-fold reduction in the 3D mammosphere diameter as compared to PAL, along with higher apoptosis and uptake efficiency. Immunofluorescence assays depicted an upregulation of BAX and downregulation of Bcl2 protein expression. In the cell cycle study, the RR-PAL-NPs showed remarkable G0/G1 phase arrest due to the decreased phosphorylation of retinoblastoma protein.

Cetirizine hydrochloride, an antihistamine drug, demonstrated potential off-label use for management of androgenic alopecia (Aga). The aim of the current study was cost-effective preparation of niosomal and cubosomal gels containing Cetirizine hydrochloride for enhanced skin permeation. Niosomes were prepared using a lipid mixture (Span 60 or Tween 80 and cholesterol), with incorporation of an essential oil (Eucalyptus or Peppermint oil) at different weight ratios. Cubosomes were prepared using glyceryl monooleate and Poloxamer 407 at different weight ratios. The prepared nanovesicles were characterized in terms of particle size, polydispersity index, zeta potential, morphological properties, entrapment efficiency, in-vitro drug release, Fourier-transform infrared spectroscopy and differential scanning calorimetry. The optimal formulations were incorporated into Carbopol gel base (1%) and evaluated in terms of organoleptic properties, viscosity, spreadability, drug permeation, and skin irritation. Niosomes and cubosomes displayed nanosized spherical and cubic morphologies, respectively, with higher entrapment efficiency for cubosomes (98 ± 4.90-99.20 ± 4.46%) compared to niosomes (40.70 ± 1.57-85.90 ± 3.19%). Ex-vivo permeation studies over 24 h demonstrated superior skin permeation for the cubosomal gel (6.2-fold increase) when compared to the niosomal gels (3.1-4.6-fold increase). Cetirizine niosomal (NG10) and cubosomal (CG6) gels demonstrated acceptable skin permeation and safety profiles thus they have great potential in off-label management of Aga.