Pharmaceutical Development and Technology最新文献

Neutrophillic asthma, characterized by persistent airway inflammation and poor corticosteroid responsiveness, presents a significant therapeutic challenge. Repurposing rapamycin, an mTOR inhibitor, and simvastatin, a statin with anti-inflammatory effects, through targeted pulmonary delivery may provide a novel therapeutic strategy. A combinatorial dry powder inhalation formulation was developed by blending rapamycin and simvastatin with lactose carriers, and a Box-Behnken design was employed to optimize blending time, fine lactose content, and leucine content. Analytical characterization using FTIR, P-XRD, DSC, and SEM confirmed effective adsorption of actives onto lactose carriers with no significant drug-excipient incompatibilities. Aerodynamic evaluation demonstrated a fine particle fraction of 53.35% and 58.67% and a mass median aerodynamic diameter 2.037 µm and 4.307 µm, for simvastatin and rapamycin respectively indicating efficient pulmonary deposition. Stability studies showed acceptable stability for 6 months and in-vivo inhalational toxicity in healthy C57BL/6 mice confirmed safety. This preclinical proof-of-concept highlights the potential of localized pulmonary delivery to reduce systemic exposure while targeting inflammatory pathways in neutrophillic asthma. Further in vivo and translational studies are warranted to establish therapeutic efficacy. This approach provides a platform for repurposing simvastatin and rapamycin as an asthma treatment and addresses the unmet need in managing steroid-resistant asthma endotypes.

Nilotinib (NH), a second-generation tyrosine kinase inhibitor for chronic myelogenous leukemia (CML), exhibits poor aqueous solubility and low intestinal permeability, classifying it as a Biopharmaceutics Classification System (BCS) Class IV drug. This study aimed to enhance NH solubility and dissolution through co-crystallization, guided by computational and experimental approaches. BASF's ZoomLab™ platform was utilized for rational coformer selection using the solubility parameter difference (Δδv) method. Validation with paracetamol and posaconazole datasets established 5 MPa^0.5 as the optimal Δδv threshold. Pyroglutamic acid (PG) emerged as the most suitable coformer and was co-crystallized with NH via liquid-assisted grinding (LAG). Solid-state characterization (PXRD, DSC, FTIR, SEM) confirmed formation of Nilotinib-Pyroglutamic acid co-crystal (NH-PGCC). The co-crystal displayed significantly improved wettability and a 3.23-fold increase in solubility in 0.1 N HCl compared to pure NH. Although rapid phase transformation occurred within 3 min, PEG 6K stabilized the supersaturated state, improving dissolution. The optimized NH-PGCC capsule achieved 75% drug release in 15 min, significantly outperforming marketed formulations (Tasigna^® and Nilotirel^®) and reduction of crystallinity was less than 2% in 6 months, suggesting stability of co-crystal. This study successfully demonstrates the applicability of ZoomLab™ in coformer prediction and formulation development for solubility enhancement of poorly soluble drugs.

Rosuvastatin is a BCS class II drug effective in the management of atherosclerosis. To enhance solubility and efficacy, Rosuvastatin-β-Cyclodextrin complex-loaded chitosan nanoparticles (R-CD-CNs) were developed. β-cyclodextrin was crosslinked with Citric acid to impart stability to the inclusion complex. Rosuvastatin was incorporated into lyophilized crosslinked β-cyclodextrin by kneading method. R-CD complex was loaded into chitosan-tripolyphosphate nanoparticles. The R-CD-CNs were optimized by 3² full factorial design with independent variables Chitosan, Sodium Tripolyphosphate as crosslinking agent and their effects were checked on dependent variables. Optimized R-CD-CNs showed Particle size 265 ± 17 nm, PDI 0.251 ± 0.02, EE 80 ± 7.5%, and Zeta potential +19.8 ± 3.8 mV. The results of DSC confirmed that drug gets incorporated into chitosan nanoparticles. XRD confirmed amorphous form of drug into chitosan nanoparticles. SEM study confirmed the sphericity of R-CD-CNs. The in vitro release profile was found to be 91 ± 2.5% at the end of 10 h, indicating sustained release characteristics. R-CD-CNs showed a more prominent effect compared to plain Rosuvastatin calcium and the disease control group. The synergistic effect of chitosan was confirmed by the in vivo antihyperlipidemic study. The results of stability study reveal good stability of R-CD-CNs. R-CD-CNs were developed successfully and will be helpful for the effective management of hyperlipidemia.

Patient rejection of unpalatable products can adversely affect therapeutic adherence, potentially leading to treatment failure. Taste masking is a goal in pharmaceutical development, particularly when developing formulations for paediatric patients. The use of an electronic tongue (e-tongue) enables rapid, objective, and robust taste evaluation. Its use is gaining traction in the quality assessment of pharmaceutical products. The capability of an Alpha Astree II taste-sensing system to evaluate the palatability of commercially available hyoscine butylbromide (HBB) syrup brands in South Africa, was investigated. Principal component analysis (PCA) was used to process the e-tongue data and the resultant biplots can distinguish between the taste of reference compounds and HBB syrups. The sensor values and taste screening rankings indicate the three brands exhibit a bitter-sweet taste. Brand Z has greater bitterness and sourness than brands, X and Y due to citric acid monohydrate in the formulation. Brand Y included sodium cyclamate and was the most palatable syrup. The findings indicate the e-tongue can differentiate the taste of HBB syrups when different excipients are used to alter taste. Pharmaceutical companies could use these data to improve the palatability of currently available hyoscine syrups. The E-tongue is a complementary instrument to human sensory panels used to inform product development in alignment with customer preferences.

A new delivery system for the dual loading of resveratrol and rutin (RES-RU-micelles), is described and characterized. Analyzes were carried out to determine the size parameters (mean particle size and polydispersity index) and surface electrical charge, 24 h after production and after 2 months of storage at two different temperatures (4 °C and 25 °C). In silico ADME predictions revealed striking differences in skin permeability between resveratrol (Log Kp = -5.47 cm/s) and rutin (Log Kp = -10.26 cm/s). Molecular analysis demonstrated that the contrasting physicochemical properties of RES (Log P = 2.57, TPSA = 60.69 Å) and RU (Log P = -2.11, TPSA = 269.43 Å) enable spatial segregation within the micelles. The RES is located predominantly in the hydrophobic core through hydrophobic interactions, while RU positions at the core-shell interface via hydrogen bonding with the hydrophilic components. The encapsulation efficiency achieved values above 98% for both bioactives in the dual loading. The viscoelastic profile showed that the G' was higher than the G" in the applied frequency range, demonstrating that the developed micelles are more elastic than viscous. DSC analysis showed the absence of peaks, corroborating that in no bioactive crystallization happened when loaded into the micelles. TEM analysis confirmed the morphology and shape of the produced micelles.

Harnessing the immune system, vaccines function as both prophylactic shields and precision-guided therapeutic agents, offering a promising strategy of a dual-armament approach in the fight against cancer. Previous landmark advances include identification of tumor-associated antigens (TAAs) and the development of dendritic cell vaccines and viral-vector platforms that laid the groundwork for modern personalized approaches. Cancer vaccines represent a transformative approach in oncology, harnessing the immune system to prevent, treat, or eliminate malignancies. Recent advances focus on improving the efficacy of immune responses, enhancing immunogenicity, and overcoming tumor immune evasion. Unlike conventional chemotherapy, which lacks durable immunity and often leads to relapse, cancer vaccines can induce long-term immune memory, reducing recurrence risks. They also mitigate drug resistance through adaptive immune targeting and synergize effectively with immune checkpoint inhibitors. With favorable safety profiles, reduced toxicity, and long-term cost benefits, cancer vaccines offer a precision-based alternative to traditional therapies. However, challenges such as tumor heterogeneity, immunosuppression, and high costs remain. Future research should optimize vaccine design, refine delivery systems, and explore combination strategies to maximize clinical outcomes. This review explores cutting-edge cancer vaccine platforms, including therapeutic (dendritic cell, peptide, mRNA, and viral vector-based vaccines), preventive (HPV and HBV vaccines), and combination immunotherapy strategies, while addressing, limitations and future directions in the field.

Berberine (BBR) exhibits broad antimicrobial and metabolic activities but suffers from limited bioavailability. Nanostructured lipid carriers (NLCs) can enhance oral delivery, while selenium (Se) coating may synergistically improve hypoglycemic and antiparasitic effects. This study aimed to design and evaluate the selenium-doped, berberine-loaded nanostructured lipid carriers (BBR-SeNLCs) for enhanced absorption, tissue diffusion, and antiparasitic efficacy against Cryptosporidium parvum in an immunosuppressed mouse model. BBR-SeNLCs were prepared via hot-melt dispersion/homogenization, followed by in situ reduction to deposit elemental selenium on the nanoparticle surface. A Cryptosporidium murine infection model was established. Parasitological burden (oocyst shedding), biochemical markers (ALT and AST), immunological parameters (IFN-γ, TNF-α, IL-6, and IL-10), and TEM ultrastructure of intestinal tissues were assessed. BBR-SeNLCs demonstrated successful berberine encapsulation. Among treatments, BBR-SeNLCs achieved comparable antiparasitic effects, with a notable reduction in oocyst shedding relative to infected controls. Biochemical assays indicate formulation-dependent hepatoprotective trends, particularly in BBR-SeNLCs formulations. Immunologically, Se-containing groups (Se alone and BBR-SeNLCs) displayed a shift toward moderated inflammatory responses (reduced IFN-γ, TNF-α, IL-6) with preserved or enhanced anti-inflammatory IL-10, suggesting balanced host immunity. Parasitological and ultrastructural analyses corroborated these findings, with BBR-SeNLCs showing preserved intestinal architecture and reduced parasite burden in treated groups.

Background: This study aimed to formulate nanostructured lipid carriers loaded with tea seed or lavender oil to enhance hair regrowth via improved follicular penetration, as an alternative to conventional alopecia therapies.

Methodology: NLCs were prepared by ultrasonication of stearic acid: essential oil mixtures into an aqueous phase containing either Tween 80 or Pluronic F127 as surfactants. Particle size, polydispersity index, zeta potential and TEM were measured. In vivo efficacy was evaluated in female Wistar albino rats given selected once-daily topical NLCs for 30 days.

Key results: DLS analysis showed that formulations F2 and F5 had mean particle sizes of 165 ± 3 nm and 181 ± 6 nm, respectively, whereas the mixed-oil formulation F3 aggregated into large droplets. Zeta potentials of -65 ± 2 mV (F2) and -42 ± 3 mV (F5) confirmed excellent electrostatic stability. TEM images verified roughly spherical, core-shell nanoparticles. In the in vivo study, F2 and F5 treatments increased mean hair lengths by 120% and 132% versus placebo (p < 0.001), respectively, compared to a 116% increase with the commercial product. NLCs significantly enhanced follicular density, with the lavender oil formulation showing superior hair shaft integrity.

Conclusion: These results demonstrate that Pluronic F127-stabilized NLCs carrying natural oils possess optimal physicochemical properties and promote hair regrowth.

Nanozymes are engineered nanoparticles that mimic enzyme-like catalytic activities and have gained significant attention in bioanalytical and biomedical applications. A broad range of nanomaterials has been explored for their intrinsic catalytic properties, and with suitable optimization, these systems can exhibit enzyme-comparable activity in biological environments. Consequently, nanozymes offer substantial potential as versatile catalytic platforms in nanomedicine. This review highlights recent advances in nanozyme research, emphasizing mechanistic understanding rather than strict kinetic equivalence to natural enzymes. Fundamental catalytic principles, including electron transfer, redox cycling, and surface-confined active-site behavior, are discussed to elucidate nanozyme function in complex biological systems. Particular focus is placed on the influence of structural features, surface functionalization, and cascade catalytic architectures on the activity of metal oxide- and carbon-based nanozymes. In addition, nanozymes responsive to tumor microenvironmental stimuli such as pH, hydrogen peroxide, and glutathione are examined for targeted redox modulation. Pharmacokinetic behavior and biosafety considerations are critically evaluated, addressing unresolved concerns related to long-term toxicity and biodistribution. Overall, nanozymes represent a promising class of catalytic nanomaterials for future nanomedicine platforms, provided systematic efforts ensure mechanistic rigor, standardized evaluation, and regulatory-aligned safety assessment.

The incidence of central nervous system (CNS) disorders is rising globally, particularly as the prevalence of neurodegenerative diseases increases. The primary challenge in such cases is limited transport of therapeutics through the blood-brain barrier (BBB). Statins, widely used for hypercholesterolemia, exhibit pleiotropic neuroprotective effects; however, their therapeutic potential in CNS disorders is restricted by poor brain bioavailability with conventional routes. Intranasal (IN) delivery has long been recognized as a plausible pathway for brain targeting. This narrative review critically examines preclinical literature on IN nanocarrier-based delivery systems developed specifically for statins, with emphasis on nose-to-brain transport, formulation strategies, pharmacokinetics (PK), and neuroprotective outcomes. This work uniquely integrates a formulation-centric comparison of IN nanocarriers for statins. It highlights the potential of IN delivery, discussing the influence of carrier type, physicochemical properties, and delivery strategy on brain targeting efficiency and therapeutic relevance across different neurological indications. IN nanocarrier systems display potential to enhance statin brain delivery by bypassing the BBB and first-pass metabolism. Nevertheless, current evidence is predominantly preclinical, with significant variability in study design, pharmacokinetic reporting, and safety evaluation. Translation to clinics will require standardized nose-to-brain metrics, long-term safety studies, scalable manufacturing processes, and early regulatory alignment.