Drug Development and Industrial Pharmacy最新文献

Background: Niacinamide is a hydrophilic cosmetic ingredient whose low skin permeation and limited incorporation into conventional nanocarriers present significant challenges.

Objective: This investigation focused on developing a nanocarrier to enhance the skin permeation of niacinamide. A novel film-forming gel system incorporating these nanocarriers was proposed, and its physicochemical characteristics were evaluated.

Methods: Nanocarriers containing niacinamide (1 mg/mL) were prepared with phytantriol evaluating their physicochemical characterization, stability, antioxidant activity and skin permeation, in comparison with the active ingredient in its free form. These nanocarriers were incorporated into a film-forming gel system, using Polifil^® (6 and 8%) as the film-forming polymer. Prior physicochemical characterization of the film-forming gel system was also conducted. The formulations were prepared without the use of organic solvents, using a top-down approach.

Results: The phytantriol-based nanocarriers, regarding their physical-chemical characterization, showed a Z-average of 160 nm, a polydispersity index of 0.104, a zeta potential of -22 mV, pH of 6.6 and a niacinamide content of 100.2%, with an incorporation rate of 52.7%. These parameters remained unchanged for 30 days at room temperature. Also, the nanocarriers containing niacinamide showed significantly greater niacinamide dermal penetration (p < 0.05) compared to the free active ingredient. Phytantriol-based nanocarriers presented an improvement in antioxidant activity, assessed by DPPH and β-carotene reduction methods (p < 0.05). Finally, in the film-forming gel system, the formulation at 8%, presented rheological and bioadhesion parameters appropriate for topical use.

Conclusions: The film-forming gel with phytantriol-based nanocarriers shows promising properties for the topical application of niacinamide.

Objectives: This review aims to explore in situ gelling drug delivery systems with emphasis on formulation strategies, gelation mechanisms, administration routes, and therapeutic benefits. It also seeks to understand the role of different polymers in achieving optimal gelation and drug release profiles. Additionally, the review aims to identify current research gaps and highlight potential areas for future development and clinical translation.

Significance: In situ gels are liquid formulations that convert into gels upon exposure to physiological triggers such as pH, temperature, or ionic strength. These systems offer advantages like sustained drug release, improved bioavailability, and enhanced patient compliance. Their adaptability supports various administration routes including ocular, nasal, oral, gastrointestinal, vaginal, and bladder delivery.

Key findings: A wide range of natural, synthetic, and semi-synthetic polymers have been studied for their in situ gelation properties. Most formulations exhibit rapid gelation upon contact with biological fluids and demonstrate good physicochemical stability. Controlled and sustained drug release was observed in vitro across different polymeric systems. The inclusion of mucoadhesive agents significantly improved residence time at the site of administration and enhanced drug absorption. These systems were found to be compatible with multiple delivery routes and maintained stability under physiological conditions.

Conclusion: In situ gelling drug delivery systems represent a versatile and efficient approach for site-specific, controlled drug release. Their ability to respond to physiological stimuli and improve mucosal retention makes them a promising alternative to traditional formulations. Continued research into polymer optimization and clinical application may further expand their therapeutic potential.

Objective: This review examines the pathology and treatment of cutaneous neoplasms, highlighting the limitations of conventional therapies and the potential of gel-based drug delivery systems for the efficient treatment of localized skin cancer.

Significance: Skin cancer, including melanoma and non-melanoma types, has a growing concern in global health with increasing incidence due to UV exposure and lifestyle changes. Conventional therapies such as chemotherapy and radiation are often limited by systemic toxicity, drug resistance and poor skin barrier penetration. Gel-based drug delivery systems, including hydrogels, nanogels, and liposome gels, offer innovative solutions by improving drug stability enabling controlled release, and reducing adverse effects. These systems enhance localized treatment by improving drug retention and targeted delivery.

Key findings: Conventional treatments face challenges such as high toxicity and inefficient drug penetration. Gel-based drug delivery systems provide enhanced drug stability, controlled release, and better skin permeability. Stimuli-responsive gels, which react to environmental factors like pH and temperature, optimize drug absorption and therapeutic efficacy while minimizing side effects. These systems address key challenges in cutaneous neoplasm therapy by improving drug delivery and patient outcomes.

Conclusion: Gel-based drug delivery systems offer a promising advancement in skin cancer treatment. Their ability to enhance drug stability, provide targeted delivery, and reduce toxicity suggests a shift toward more effective and patient-friendly therapeutic strategies, ultimately improving treatment outcomes.

Objective: To perform a narrative review that critically examines the application of design thinking (DT) in pharmaceutical product development, with emphasis on its role in advancing nanomedicine innovation and patient-centric drug design.

Significance of review: DT offers a human-centered, iterative alternative to the traditional linear R&D model. Its integration into pharmaceutical development addresses challenges such as high attrition rates, limited patient input, regulatory complexity, and scalability, thereby improving translational success. This review adopts a conceptual and narrative approach, analyzing the five stages of DT, Empathize, Define, Ideate, Prototype, and Test, within the context of pharmaceutical development.

Key findings: The application of DT fosters tangible benefits in pharmaceutical innovation, including empathy-driven product design, targeted problem framing, and iterative prototyping aligned with user and regulatory needs. Case studies such as Doxil^®, ABRAXANE^®, and mRNA-based COVID-19 vaccines illustrate established successes, while emerging examples, including CRISPR-based therapeutics and extracellular vesicle (EV) nanocarriers, underscore the forward-looking potential of this methodology. Together, these examples highlight how DT accelerates development timelines, mitigates risk, and enhances patient and regulatory alignment.

Conclusions: Integrating DT into pharmaceutical product development enhances innovation by fostering interdisciplinary collaboration, reducing costs, and increasing the likelihood of successful translation to market. Its strategic application in nanomedicine provides a transformative pathway for next-generation therapies that are safer, more effective, and aligned with patient expectations and evolving regulatory frameworks.

Objective: Hot-melt extrusion (HME) has emerged as a solvent-free, scalable, efficient, and continuous process to overcome the challenges of poor solubility in new drug entities. Using HME technique, crystalline drugs are converted to amorphous solid dispersions (ASDs), which significantly enhances their dissolution rates and oral bioavailability. This review is aimed to provide a comprehensive review of HME as a transformative strategy in pharmaceutical manufacturing.

Significance of review: This review critically analyzes the mechanistic insights of solubility enhancement using HME, its advantages over traditional methods, key formulation components, and the influence of processing parameters on drug stability and performance. Moreover, translational case studies emphasizing the applications of HME in solubility enhancement, and the growing role of artificial intelligence (AI) and molecular modeling are discussed in detail. It also covers the patent landscape relevant to HME and compares HME with other methods of ASD preparation.

Key findings: The literature indicated that recent technological advancements in HME including nanocrystal generation, co-crystallization, hybrid methods, and three-dimensional printing integration garners its immense potential and highlighting its wide scope of applications. Recent integration of AI and machine learning (ML) with HME has emerged as a forward-looking strategy that can be employed successfully in the optimization of formulation design and manufacturing.

Conclusions: The continuous processing capabilities, adaptability to various dosage forms, and compatibility with modern drug development strategies have highlighted the importance and versatile applications of HME. Moreover, growing regulatory acceptance and continuous innovations have placed HME at the forefront of pharmaceutical development for poorly soluble compounds.

Objective: This review aims to explore advanced nanotechnology-integrated delivery systems designed to facilitate the transport of therapeutic agents across the blood-brain barrier (BBB) for the treatment of central nervous system (CNS) disorders, particularly neurodegenerative diseases.

Significance: CNS disorders remain a primary global health concern due to their progressive nature and limited treatment options. Conventional therapies exhibit minimal efficacy, primarily due to the restrictive nature of the BBB, which impedes drug access to brain tissue. Overcoming this barrier is crucial to improving therapeutic outcomes and minimizing systemic side effects.

Methods: A comprehensive analysis of nanotechnology-based approaches was conducted, focusing on the physicochemical properties of nanocarriers, their interactions with the BBB, and their roles in targeted drug delivery. Strategies involving nanoparticle engineering, ligand-functionalized systems, and gene delivery vectors were critically reviewed.

Results: Nanotechnology has shown considerable promise in facilitating drug delivery across the BBB. Nano-engineered platforms are capable of targeting specific cells, modulating signaling pathways, enhancing neuronal survival, and even inducing regeneration. Various successful nanocarriers, including liposomes, dendrimers, polymeric nanoparticles, and exosomes, demonstrate enhanced drug penetration and specificity.

Conclusions: Nanotechnology holds transformative potential in treating CNS disorders by addressing the limitations posed by the BBB. Continued research into the design and optimization of brain-targeted nano-systems holds the key to safer, more effective therapies. The manuscript also highlights current challenges and considerations in developing such delivery systems for clinical application.

Objective: To prepare astragaloside IV dripping pills (ASDP) and assess their therapeutic effects on mice with doxorubicin hydrochloride-induced dilated cardiomyopathy (DCM). Significance: Astragaloside IV (AS) exhibits pharmacological effects in treating cardiovascular diseases, however, its clinical application is hindered by poor solubility and low bioavailability. The study sheds light on new therapeutic strategy of DCM and development of AS formulations. Methods: The ASDP prepared by solid dispersion technology were optimized and characterized through scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC), as well as evaluations of appearance, average weight, hardness, disintegration time, drug content, solubility and dissolution behavior. The therapeutic effects of ASDP on mice with doxorubicin hydrochloride-induced DCM were performed via echocardiography, heart weight index measurements, pathological examination of heart tissues, and determination of serum levels of angiotensin II (Ang II), B-type natriuretic peptide (BNP), and suppressor of tumorigenicity 2 (ST2). Results: ASDP presented as round, white pills with an average weight of 27.61 mg, a short disintegration time (approximately 3 min), a hardness of 4.9 ± 0.2 N and drug content of 64.5 ± 0.12mg/g. Compared to AS, ASDP significantly improved solubility and dissolution rate. In the doxorubicin hydrochloride-induced DCM mouse model, ASDP alleviated cardiac dysfunction and hypertrophy, reduced necrosis, and decreased serum levels of Ang II, BNP and ST2. Conclusion: ASDP, which enhance the solubility and dissolution of AS, demonstrate significant therapeutic efficacy against DCM, suggesting their potential as a promising candidate for DCM treatment.

Objective: In order to optimize the extraction of Teucrium polium (TP) and chicken bile (Bi), evaluate their biological activities and formulate a micro-emulgel for hemorrhoidal therapy.

Significance: Teucrium polium and chicken bile have been historically valued for their traditional medicine for treating hemorrhoids. Therefore, they were used for the development of pharmaceutical formulation.

Methods: A Box-Behnken Design (BBD) was employed to determine the optimal extraction parameters for Teucrium polium, including ethanol/water ratio, extraction time, and material/solvent ratio as factors. The biological activities of both TP and Bi extracts, including antioxidant, antibacterial and anti-inflammatory properties were assessed. The simplex lattice design was used to optimize the formulation of micro-emulgel of both extracts by studying the effect of the surfactant/co-surfactant ratio as well as the oil and water on the spreadability and viscosity of the micro-emulgel. The micro-emulgel was then characterized.

Results: The Teucrium polium extract demonstrated strong antioxidant and antimicrobial activities, while chicken bile exhibited remarkable anti-inflammatory effect. The optimal micro-emulgel had a good consistency and stability.

Conclusion: These findings suggest the potential for these natural extracts to be formulated into topical therapies for hemorrhoidal treatment, supporting their traditional use in medicine.

Objective: To provide a comprehensive evaluation of mucilage-based nanocarriers as emerging platforms for targeted cancer therapy, focusing on their design, functionalization, and therapeutic potential.

Significance: Mucilage, a plant-derived biopolymer composed of natural polysaccharides, possesses inherent biocompatibility, biodegradability, and unique physicochemical characteristics such as high-water retention, gel-forming ability, and stimuli-responsiveness. These properties position mucilage as an ideal material for controlled drug delivery in oncology, offering potential improvements over conventional nanocarriers. However, despite these advantages, the application of mucilage in nanocarrier design remains underexplored, with limited consolidation of existing knowledge and comparative performance data-representing a significant research gap in the field of natural polymer-based drug delivery systems.

Methods: This review synthesizes current advances in the fabrication and functionalization of mucilage-based nanocarriers using techniques such as emulsion solvent evaporation, nanoprecipitation, and green synthesis. It also examines surface modifications, including ligand conjugation and pH-sensitive linker integration, aimed at enhancing tumor-targeted delivery and intracellular drug release.

Results: Preclinical studies demonstrate that mucilage-based nanocarriers enable efficient encapsulation of hydrophobic drugs, improve solubility and pharmacokinetic profiles, and promote targeted drug accumulation at tumor sites. These systems show prolonged circulation times and reduced systemic toxicity compared to traditional nanocarriers.

Conclusions: This review highlights the novelty of mucilage-based systems as a sustainable and multifunctional nanoplatform for cancer therapy. While demonstrating clear therapeutic potential, these systems face challenges including variability in mucilage composition, scalability of production, long-term stability, and regulatory standardization. Future efforts should focus on developing standardized extraction methods, predictive design models, and fostering multidisciplinary collaborations to fully realize the clinical potential of these systems in precision oncology.

Objective: The current study aimed to formulate naringenin nanoparticles (NNPs) with chitosan polymer and investigate their protective effect against cognitive deficit induced by streptozotocin (STZ) in swiss albino mice.

Methods: The interactions of naringenin with the possible targets involved in the pathogenesis of cognitive deficit were predicted using AutoDock vina and predicted its absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties with SwissADME and ProTox-II web servers. NNPs were formulated with chitosan using the ionotropic gelation method and coated with tween 80. The cognition functions of NNPs were evaluated by Elevated Plus Maze (EPM) and Novel Objective Recognition test (NORT) in STZ-induced cognitive deficit in mice at doses 50 and 100 mg/kg equivalent to pure drug, i.p. The effect of NNPs on various antioxidant enzymes (glutathione, superoxide dismutase, catalase, and mitochondrial complexes (1-4)) in cortex and hippocampus region of the brain was also estimated by biochemical methods.

Results: In silico study revealed better binding interactions as well as good binding affinity of naringenin with all the studied targets compared to rivastigmine. The formulated coated NNPs displayed good drug entrapment efficiency (75.412%) and a good in vitro release that followed the Korsmeyer-Peppas model (R² = 0.962). Furthermore, in-vivo studies displayed a learning and memory-enhancing effect of NNPs in EPM and NORT models compared to naringenin alone. A significant increase in the level of antioxidant enzymes revealed that the protective effects of naringenin nanoformulation might be mediated by its potent antioxidant and mitochondrial restoring properties.

Conclusion: Collectively, these studies suggested that the nanoformulation of naringenin is worthwhile for the management of cognitive improvement and other neurological problems.