Therapeutic delivery最新文献

Aims: The present investigation aimed at the comparative evaluation of the developed nanocarriers, viz. spherulites and cubosomes for lung targeting.

Materials and methods: Both the spherulites and cubosomes were characterized for their entrapment efficiency, drug loading, size and zeta potential, in-vitro drug release profile, surface morphology, hemocompatibility, and in-vivo pharmacokinetic and lung biodistribution.

Results and conclusions: The optimized batches of spherulites and cubosomes possessed high entrapment efficiency and drug loading with size around 200 nm, which is suitable for lung targeting. The zeta potential value for both the nanoformulations was found to be between -20 and -30 mv indicating the physical stability against aggregation. The SEM and TEM analysis revealed the presence of spherical and discrete particles in both the types of nanocarriers. Water channels were observed in case of cubosomes. Spherulites and cubosomes showed pH-dependent drug release with lower release at physiological pH while higher release at the pH of the tumor microenvironment. Both spherulites and cubosomes exhibited highly significant increase in the half-life and mean residence time in the plasma. The prepared nanoformulations were hemocompatible and had higher lung targeting potential compared to the plain drug solution.

Background: The integration of immunotherapy alongside chemotherapy represents a crucial approach in the treatment of cancer. Herein we report the SN-38-indoximod conjugate nano-prodrug to address the difficulties encountered by individuals. In this prodrug, SN-38 is connected to indoximod through a specific disulfide linker, which enables the release of the components in response to the tumor microenvironment characterized by elevated levels of glutathione, thereby facilitating programmed chemoimmunotherapy.

Results: SN-38-indoximod conjugate was synthesized and fabricated to nano-prodrug by reprecipitation method. It showed comparable anti-cancer activity against A549 cells than SN-38 (IC₅₀ = 0.24 ± 0.01 µM) with IC₅₀ value 0.32 ± 0.04 µM. It inhibited 90% A549 cell at very lower concentration (IC₉₀ = 6.07 ± 0.41 µM) as compared with SN-38 (IC₉₀ = 24.60 ± 1.24 µM) and mixture of SN-38: indoximod (1:1, IC₉₀ >30 µM). The nano-prodrug showed better size distribution profile and dispersion stability contains nanoparticles in effective size range (80-160 nm) required for the EPR effect.

Conclusion: This research offers valuable insights into the advancement of conjugate nano-prodrugs exhibiting synergistic pharmacological effects, while also presenting novel opportunities for the design of prodrug molecules capable of releasing drugs in response to diverse triggers.

Aim: Abemaciclib (ABE) is an anticancer drug that suffers from low bioavailability and multidrug resistance. This study aims to develop ABE-loaded solid lipid nanoparticles (ABE-SLNs), which will enhance drug solubility and lead to increased cellular uptake and enhanced cytotoxicity when delivering tumor cells.

Methods: Melt emulsification followed by ultrasonication was used as a method of preparation and Quality-by-Design (QbD) was utilized to optimize ABE-SLNs.

Results: The optimized ABE-SLNs consist of Precirol-ATO5 as a lipid and Brij-58 as a surfactant. The particle size, PDI value, and zeta potential of the optimized formulation were 170.4 ± 0.49 nm, 0.25 ± 0.014, and -26.4 ± 0.1 mV, respectively. It also showed sustained release behavior and a high entrapment efficiency of 79.96%. ABE-SLNs exhibited enhanced anticancer activity in the MDA-MB-231 and T47D breast cancer cell lines compared to pure ABE. In Caco-2 human colonic cell lines, ABE-SLNs also showed increased cellular uptake.

Conclusion: The use of QbD to achieve high entrapment efficiency and sustained release in ABE-SLNs, coupled with enhanced cellular uptake and cytotoxicity, represents a novel approach that could set a new standard for nanoparticle-based drug delivery systems.

Aim: Development and optimization of raloxifene hydrochloride loaded lipid nanocapsule hydrogel for transdermal delivery.

Method: A 3³ Box-Behnken Design and numerical optimization was performed to obtain the optimized formulation. Subsequently, the optimized raloxifene hydrochloride loaded lipid nanocapsule was developed using phase inversion temperature and characterized for physicochemical properties. Furthermore, the optimized lipid nanocapsule was loaded into a hydrogel and evaluated for rheology, spreadability, ex-vivo skin permeation, deposition and irritation.

Results: The numerical optimization suggested an optimal formula with desirability value of 0.852 and low prediction errors. The optimized formulation showed good % drug entrapment efficiency (79.56 ± 2.34%), nanometer size (56.68 ± 1.2 nm), monodisperse nature (PDI = 0.176 ± 0.2), spherical morphology and good drug-excipient compatibility. The raloxifene hydrochloride loaded lipid nanocapsule hydrogel showed shear thinning properties, sustained drug delivery, dermal compatibility and significantly higher permeability (2-fold), retention (3.37) for raloxifene hydrochloride compared to the control.

Conclusion: The present study showed a successful development of raloxifene hydrochloride loaded lipid nanocapsule hydrogel with improved skin permeation, retention, and good topical compatibility. This formulation may overcome the challenges associated with raloxifene hydrochloride oral delivery including low bioavailability.

Aim: The study aimed to formulate solid lipid nanoparticles (SLNs) for the transdermal delivery of PPL to improve skin retention and efficacy.

Materials and method: The particle size distribution of SLNs was determined and the morphology of SLNs was also analyzed by SEM. In-vitro, ex-vivo and in vivo evaluations were done for PPL loaded SLN. The safety of drug delivery systems was assayed using MTT test.

Results: The results indicated successful encapsulation of PPL in SLNs (59.38%), which exhibited a spherical shape and smooth surface. Compared to PPL solution, SLNs demonstrated a prolonged drug release profile in vitro. Stability tests over three months showed no significant changes in entrapment efficiency or size distribution. Enhanced permeation through shed snake and rat skin was observed with SLNs compared to the PPL solution. Ex-vivo and in vivo studies confirmed that PPL-loaded SLNs significantly increased drug content in the skin. Importantly, the SLNs displayed biocompatibility, as no significant cytotoxic effects were noted, and they were nonirritating to rat skin.

Conclusion: To the best of our knowledge, this is the first study that indicates SLNs can be considered as a promising nanocarriers for transdermal delivery of PPL.

Natural hydrogels have garnered increasing attention due to their natural origins and beneficial roles in wound healing. Hydrogel water-retaining capacity and excellent biocompatibility create an ideal moist environment for wound healing, thereby enhancing cell proliferation and tissue regeneration. For this reason, naturally derived hydrogels formulated from biomaterials such as chitosan, alginate, gelatin, and fibroin are highly promising due to their biodegradability and low immunogenic responses. Recent integrated approaches to utilizing new technologies with bioactive agents have significantly improved the mechanical properties of hydrogels and the controlled release and delivery of active compounds, thereby increasing the efficiency of the treatment processes. Herein, this review highlights the advantages and the challenges of natural hydrogels in wound healing, focusing on their mechanical strength, controlled degradation rates, safety and efficiency validation, and the potential for incorporating advanced technologies such as tissue engineering and gene therapy for utilization in personalized medicine.

Orodispersible film (ODF) is one of the novel formulations that disintegrate rapidly in the mouth without the requisite for water compared to other conventional oral solid dosage formulations. This delivery system serves as a convenient mode of administration, especially in patients who have dysphagia and fluid restriction, being beneficial to pediatric, geriatric, and bedridden patients. A novel sildenafil ODF containing sildenafil citrate is formulated to be used in patients with erectile dysfunction (ED). This review discusses the advantages of ODF in improving compliance and satisfaction in these patients and describes the manufacturing techniques, evaluation tests, bioequivalence, and stability studies of sildenafil ODF. This formulation offers unique benefit to patients with ED by improving their acceptance and compliance and respecting their privacy and the need for a discreet treatment. Moreover, the comparison of pharmacokinetic parameters between the sildenafil ODF administered with and without water and the conventional film-coated tablet were similar. It also demonstrated reliable performance that yielded a consistent product, meeting all specifications at release and after three weeks of storage under stressed conditions (60°C). Sildenafil ODF warrants improved ease of intake, taste, portability, storage, and compliance among ED patients, making it the potential most preferred formulation and drug of choice.

An established view in genetic engineering dictates an increase in the discovery of therapeutic peptides to enable the treatment of multiple diseases. The use of hypodermic needle for delivery of proteins and peptides occurs due to the hydrophilic nature, sensitivity toward proteolytic enzymes and high molecular weight. The non-invasive nature of the transdermal delivery technique offers multiple advantages over the invasive route to release drugs directly into the systemic circulation to enhance bioavailability, better patient compliance, reduced toxicity and local irritability. The transdermal route seems highly desirable from the pharmaco-therapeutic and patient compliance point of view, however, the lipophilic barrier of skin restricts the application. The use of several techniques like electrical methods (iontophoresis, sonophoresis etc.), chemical penetration enhancers (e.g. protease inhibitors, penetration enhancers, etc.) and nanocarriers (dendrimers, lipid nanocapsules, etc.) are utilized to improve the passage of drug molecules across the biomembranes. Additionally, such clinical interventions facilitate the physicochemical characteristics of peptides, to enable effective preservation, conveyance and release of therapeutic agents. Moreover, strategies ensure the attainment of the intended targets and enhance treatment outcomes for multiple diseases. This review article focuses on the techniques of peptide transportation across the skin to advance the delivery approaches and therapeutic efficiency.

Aim: The goal of the present work was to formulate zein-decorated rifaximin (RFX) nanosuspension to attain sustained release as well as effectiveness against Escherichia coli (E. coli).Methods: The RFX nanosuspension was fabricated by using antisolvent addition method followed by coating using hydroalcoholic zein solution. The optimized RFX-NS and RFX-NS@zein was lyophilized for further spectroscopic evaluations. In vitro antibacterial potential was elucidated using well diffusion method whereas MIC value was determined by microbroth dilution method against E. coli for RFX-NS and pure RFX.Results: Box-Behnken Design was employed to assess the effects of independent variables on quality target product profile of RFX-NS. Optimized RFX-NS depicted particle size of 193.5 ± 4.45 nm with 76.49 ± 1.71% drug content. The significant change in particle size and zeta potential confirmed the formation of zein coated RFX-NS (RFX-NS@zein). In vitro release study depicted, 96.91 ± 1.21% release of RFX from RFX-NS in 6 h whereas 97.47 ± 1.99% RFX release was observed from RFX-NS@zein at the end of 12 h. Antibacterial assay of RFX-NS and free RFX against E. coli displayed MIC value of 15.44 ± 0.01 μg/ml and 72.96 ± 0.25 μg/ml, respectively.Conclusion: The results highlighted a significance of nanosuspension for improving the solubility of RFX and its antibacterial potential against E. coli.

Aims: To enhance the therapeutic potential of Cabozantinib (CBZ), a tyrosine kinase inhibitor with limited water solubility, low bioavailability, and high toxicity, by developing a Cabozantinib-Phospholipid Complex (CBZ-PLS).

Materials & methods: CBZ-PLS was formulated using solvent evaporation with a Box-Behnken design and characterized using various techniques to confirm molecular interactions. Solubility, in vitro release, pharmacokinetics, and toxicity were evaluated. Cytotoxic effects on HepG2 cell lines were also assessed.

Results: CBZ-PLS exhibited a 126-fold increase in solubility and enhanced CBZ release in vitro. Pharmacokinetic studies on Wistar rats demonstrated a 1.58-fold increase in bioavailability, while acute toxicity studies confirmed biocompatibility. CBZ-PLS showed superior cytotoxicity, apoptosis induction, migration inhibition, increased ROS generation, and greater DNA fragmentation in HepG2 cells. The complex also maintained stability over 6 months.

Conclusions: CBZ-PLS significantly improves the solubility, bioavailability, and therapeutic efficacy of CBZ against liver cancer, presenting a promising approach for more effective liver cancer treatment.