Drug Development and Industrial Pharmacy最新文献

Objective: This review aims to evaluate the therapeutic potential of Risperidone (RSP)-loaded nanoparticles as an innovative drug delivery approach for effective schizophrenia (SZ) management and improved patient outcomes.

Significance: Schizophrenia is a long-standing mental disorder involving disturbances in thought, perception, and behavior, frequently necessitating extended pharmacologic therapy. While RSP, a second-generation antipsychotic, is efficacious against both positive and negative symptoms, its therapeutic use is impaired by limited water solubility, low oral bioavailability, extensive first-pass metabolism, and dose-dependent side effects. Overcoming these limitations may substantially benefit patient outcomes. Recent advances in nanotechnology have allowed the development of several RSP-loaded nanocarriers such as polymeric nanoparticles, solid lipid nanoparticles, and nanostructured lipid carriers.

Key findings: This review evaluates these systems according to drug loading efficiency, release kinetics, brain-targeting capacity, and drug administration routes, according to preclinical data. RSP nanoparticles exhibited improved solubility, sustained release, enhanced brain targeting, and decreased systemic toxicity. Intranasal and parenteral routes are additional advantages in enhancing bioavailability and compliance in non-compliant patients. Such formulations provide improved pharmacokinetic profiles and reduce extrapyramidal symptoms.

Conclusion: RSP-loaded nanoparticles are a valuable innovation in SZ therapy through enhancing efficacy, minimizing side effects, and improving patient compliance. More clinical studies are warranted to determine their safety, long-term efficacy, and commercial viability for translation into the clinic.

Objective: This study aimed to develop, characterize, and evaluate resveratrol-loaded pegylated PLGA [poly (lactic-co-glycolic acid)] nanoparticles with folate conjugation for improved drug delivery and cytotoxic efficacy against MCF7 breast cancer cells.

Significance: The significance of this drug delivery system is to enhance the wetting characteristics of resveratrol and reduce nanoparticle agglomeration for maximizing therapeutic efficacy while minimizing systemic cytotoxicity using PLGA and polyethylene glycol (PEG) polymeric nanoparticles as carriers. The process of fabrication and characterization of polymeric conjugate by utilizing PLGA-PEG surface engineered with folic acid for target specificity has already been investigated.

Methods: Nanoparticles were prepared by double-emulsion solvent evaporation using PPF (PLGA-PEG-FOLATE conjugate polymer) and PVA (Poly vinyl alcohol) as a stabilizer. Compatibility studies were performed using FTIR, DSC, and XRD. Formulations (NF1-NF8) were evaluated for particle size, zeta potential, drug loading, entrapment efficiency, and in vitro release. Surface morphology was assessed by SEM and TEM. MTT assay evaluated cytotoxicity while fluorescence microscopy analyzed cellular uptake.

Results: Compatibility studies confirmed no drug-excipient interactions. NF3 exhibited optimal characteristics: particle size 332.1 nm, zeta potential -24.6 mV, entrapment efficiency 78.65 ± 0.165%, and drug loading 36.19 ± 0.154%. In vitro release was sustained up to 120 h (75.17 ± 0.22%), fitting zero-order kinetics with Fickian diffusion. NF3 displayed enhanced cytotoxicity (IC50 340.26 nM) compared to free resveratrol (993.29 nM). Fluorescence microscopy confirmed improved cellular uptake via folate conjugation.

Conclusion: Resveratrol-loaded PPF nanoparticles, particularly NF3, demonstrated superior stability, sustained release, and enhanced anticancer activity, making them a promising candidate for targeted breast cancer therapy.

Significance: Raloxifene hydrochloride (RH) treats osteoporosis in postmenopausal women. However, due to its limited bioavailability efforts have been focused on enhancing its solubility and bioavailability.

Objective: In this study in situ micronization have been explored to improve drug solubility through reducing particle size and enhancing saturation solubility, dissolution rate, and pharmacokinetic properties.

Methods: D-α-tocopheryl polyethylene glycol succinate (TPGS), Solotul HS15, Cremophor^® CO40, and HPMC K4M were chosen as solubility enhancing agents to produce nanocrystals via the solvent change method. The study assessed particle size, saturation solubility, and drug release rate across different formulations containing various stabilizers and concentrations.

Results: Nanoparticles stabilized by 0.1% TPGS depicted the smallest particle size (467.60 ± 37.89 nm), the highest drug release in 2 h (99.61 ± 6.72%) and saturation solubility (834.11 ± 16.73 µg/mL) in comparison to pure RH and other stabilizers. Nanoparticles of RH showed C_max of 1.86 ± 1.1 µg/mL compared to the pure crystals of RH, which showed maximum serum concentration of 0.52 ± 0.68 µg/mL. The AUC_0-24 was also inclined about four times more in nanoparticles compared to the pure drug while T_max was the same in both groups.

Conclusions: The obtained results demonstrated in situ micronization technique by solvent change method was successful in improving RH bioavailability.

Objective: To develop and evaluate a scalable, multidrug-releasing intrauterine device (IUD) capable of treating common gynecological infections caused by viral, bacterial, and fungal pathogens.

Significance: Women's health encompasses both physical and emotional well-being and is impacted by inequitable access to advanced healthcare technologies. Conditions such as genital herpes, bacterial vaginosis (BV), and vulvovaginal candidiasis (VVC) are prevalent and often managed with systemic oral drugs, which can reduce patient compliance and treatment efficacy due to side effects and dosing challenges. A localized, sustained-release IUD could improve adherence and therapeutic outcomes.

Methods: An IUD was manufactured using injection molding with high-density polyethylene (HDPE) due to its biocompatibility. Devices were loaded with acyclovir and silver sulfadiazine, with actual drug incorporation measured at ∼2%-3% w/w for single or combination formulations. Physical-chemical, mechanical, and in vitro drug release tests were conducted to evaluate feasibility and performance.

Results: The injection molded HDPE-based IUD demonstrated sustained drug release and structural integrity. Initial in vitro results confirmed the capability to release multiple agents over time, although drug loading efficiency remains an area for improvement.

Conclusions: This approach presents a promising, scalable strategy for localized treatment of gynecological infections. Further optimization and in vivo studies are warranted to validate the device's therapeutic effectiveness and regulatory readiness.

Objective: This study aimed to fabricate a delayed-release tablet of Mebeverine hydrochloride using a novel dual extrusion-based 3D printing approach to improve the management of irritable bowel syndrome (IBS).

Significance: This study highlights a dual extrusion-based 3D printing approach that integrates a hydrogel core of Mebeverine hydrochloride with a melt-extruded polymeric shell in a single step, protecting from acidic and thermal stress while achieving controlled release. The 3D-printed tablet meets USP quality standards, demonstrating a promising strategy for IBS management and personalized therapy.

Methods: The tablet design combines a drug-loaded hydrogel core with a melted extruded polymeric shell, created simultaneously in a single printing process. While the shell formed through melt extrusion (ME) using an optimized blend Kollidon^® VA 64, PEG 4000, HPMCP, Eudragit RL100, triethyl citrate, and talc, the hydrogel core methylcellulose, sodium alginate, sodium chloride, and the drug, deposited into the internal cavity by pressure-assisted micro-syringe (PAM) extrusion.

Results: The resultant tablet limited drug release in acidic circumstances while achieving 98.6% drug release over 12 h in phosphate buffer. Weight variation, friability, hardness, assay, and content uniformity met USP specifications. SEM imaging indicated smooth and consistent surface morphology. Moreover, FTIR spectrums showed no unwanted chemical interactions, TGA and DSC analysis verified the thermal stability the drug and excipients at printing temperatures.

Conclusions: The dual extrusion based-3D printing of drug-loaded hydrogel and thermoplastic polymers provides a promising delayed-release single dosage to deliver of thermo- and acid-labile drugs for the management of IBS and associated gastrointestinal disorders.

Objectives: Breast cancer remains the most frequently diagnosed cancer worldwide and the second leading cause of cancer-related mortality among women. Drug resistance and significant adverse effects limit anticancer drugs efficacy despite their availability. Oxaliplatin (OXA), a platinum-based chemotherapeutic agent, has shown potential in metastatic breast cancer, however, its toxicity limit its use. Melatonin (MEL) demonstrates anticancer activity and improves chemotherapy efficacy, but its therapeutic use is limited by poor stability and short half-life. Nanocarriers, particularly lipid-polymer-hybrid nanoparticles (LPNs), offer an innovative approach to improve drug delivery, enhance bioavailability, and limited systemic toxicity.

Methods: OXA and MEL co-encapsulated LPNs were prepared. Design of Experiments (DoE)-based optimization was employed using the Box-Behnken design (BBD) to systematically evaluate critical formulation parameters. Particle size, polydispersity index, zeta potential, encapsulation efficiency, release, FTIR, DSC, and stability studies were carried out. The effects of OXA-MEL-loaded-LPNs were assessed on human breast cancer cell line (MCF-7).

Results: Optimized LPNs exhibited a particle size of ∼240 nm, PDI of 0.17, zeta potential of -30 mV, and encapsulation efficiencies of 99.1% for MEL and 96.1% for OXA. In vitro release studies showed sustained release, with ∼26% OXA and ∼18% MEL released over 8 h. FTIR and DSC analysis showed all substances were loaded into particles. Stability data indicate that particle size remains within the acceptable range for up to one week. Lyophilization resulted in a slight increase in particle size and PDI. Co-loaded LPNs exhibited significant cellular cytotoxicity.

Conclusion: The findings suggest that LPNs offer a promising platform for combination therapy, potentially improving treatment outcomes in breast cancer.

Objective: This review investigates the advancements of nanocarrier-based chemotherapeutic agents from their inception to present-day implementation. It focuses on the types of nanocarriers introduced to date, the FDA-approved nanomedicines and the nanomedicines undergoing clinical trials, and particularly discusses how nanomedicine overcomes many biochemical, biophysical, and biomedical barriers whose efficacy far exceeds other conventional drug delivery systems (DDS).

Significance: This review highlights the unique ability of nanocarriers that improve the solubility of drugs, effectively transporting and accumulating large drug doses specifically to tumor cells, destroying them, and exploiting the erratic tumor microenvironment (TME) due to defective angiogenesis by cancer cells, setting nanocarriers apart from conventional DDS.

Key findings: Nanomedicines like Doxil rely on passive targeting and are effective only in solid tumors, displaying the Enhanced Permeability and Retention (EPR) effect. Therefore, different approaches are taken to improve the EPR effect in metastatic cancer through active targeting. Nanomedicine circumvents efflux transporters and reduces multidrug resistance. Aside from being used as a medium for anti-cancer agents, nanocarriers can also be used for cancer immunotherapy, gene therapy, and diagnostic purposes.

Conclusion: Nanomedicines enhance drug delivery, reduce toxicity, and improve the therapeutic efficacy in cancer therapy. Nanomedicine also aids in cancer imaging and enables advanced immunotherapy and gene therapy. These innovations can lead to more effective, personalized cancer treatments with fewer side effects. However, nanocarriers still has some limitations and challenges such as its own toxicity, payload issues and immunogenic reactions, which are further needed to be improved.

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.