Drug Development and Industrial Pharmacy最新文献

Objectives: This research aimed to overcome challenges posed by cefepime excessive elimination rate and poor patient compliance by developing transdermal delivery system using nano-transfersomes based chitosan gel.

Methods: Rotary evaporation-sonication method and the Box-Behnken model were used to prepare cefepime loaded nano-transfersomes (CPE-NTFs). The physiochemical characterization of CPE-NTFs were analyzed including DLS, deformability index, DSC and antimicrobial study. Optimized CPE-NTFs loaded into chitosan gel and appropriately characterized. In vitro release, ex vivo and in vivo studies were performed.

Results: The CPE-NTFs were physically stable with particle size 222.6 ± 1.8 nm, polydispersity index 0.163 ± 0.02, zeta potential -20.8 ± 0.1 mv, entrapment efficiency 81.4 ± 1.1% and deformability index 71 ± 0.2. DSC analysis confirmed successful drug loading and thermal stability. FTIR analysis showed no chemical interaction among the excipients of CPE-NTFs gel. The antibacterial activity demonstrated a remarkable reduction in the minimum inhibitory concentration of cefepime when incorporated into nano-transfersomes. CPE-NTFs based chitosan gel (CPE-NTFs gel) showed significant physicochemical properties. In vitro release studies exhibited sustained release behavior over 24 h, and ex vivo studies indicated enhanced permeation and retention compared to conventional cefepime gel. In vivo skin irritation studies confirmed CPE-NTFs gel was nonirritating and biocompatible for transdermal delivery.

Conclusion: This research showed nano-transfersomes based chitosan gel is a promising approach for cefepime transdermal delivery and provides sustained release of cefepime.

Objective: This research aimed to investigate the application of the coaxial electrospun method for the production of natural extracts (papaya leaf extract) fibre films. This was achieved through utilising different polymers and with a focus on the conductivity and the viscosity of polymer solutions as critical parameters to generate successful fibres.Significance: Electrospinning is a promising trending manufacturing method for incorporating thermolabile herbal extracts using coaxial electrospun features. However, the complexity of the electrospinning process and the feasibility of the product required precise scrutiny.Methods: The electrospinning solution parameters (conductivity and viscosity) were evaluated by employing various ratios of Eudragit L100 (EL100) and Eudragit L100-55 (EL100-55) pre-spinning polymeric blend solutions. The electrospinning process and ambient parameters were optimised. Following that, the in-silico physicochemical properties of phytochemical marker, rutin, were illustrated using SwissADME web tool. Both freeze-dried Carica papaya leaf extract and its produced films were characterised using Scanning Electron Microscopy (SEM), Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR), polarised light microscopy, and X-ray Powder Diffraction (XRPD).Results: The optimal values of conductivity (≈40-44 × 10^-4 S/m) and viscosity (≈32-42 × 10^-3Pa·s) were determined for producing evenly distributed and small fibre diameters in SEM images. These parameters significance was highlighted in acquiring and maintaining adequate tangential stress for fibre elongation, which would consequently affect the morphology and diameter of the fibres formed.Conclusion: In conclusion, the solution, process, and ambient parameters are significant in developing natural extracts into films via electrospinning technology, and this includes the promising Carica papaya leaf extract films produced by coaxial electrospinning.

Objectives: To develop and evaluate a novel human stratum corneum (SC) mimetic phospholipid vesicle-based permeation assay (PVPA_SC) model for in vitro permeation studies.

Significance: Due to the increasing restrictions on the use of human and animal skins, artificial skin models have attracted substantial interest in pharmaceuticals and cosmetic industries. In this study, a modified PVPA_SC model containing both SC lipids and proteins was developed.

Methods: The PVPA_SC model was optimized by altering the lipid composition and adding keratin in the formulation of large liposomes. The barrier properties were monitored by measuring the electrical resistance (ER) and permeability of Rhodamine B (RB). The modified PVPA_SC model was characterized in terms of the surface topography, solvent influence and storage stability. The permeation studies of the active components in Compound Nanxing Zhitong Plaster (CNZP) were performed to examine the capability of PVPA_SC in the application of skin penetration.

Results: The ER and P_app values of RB obtained from the optimized PVPA_SC model indicated a similar barrier property to porcine ear skin. Scanning electron microscope analysis demonstrated a mimic 'brick-and-mortar' structure. The PVPA_SC model can be stored for three weeks at -20 °C, and withstand the presence of different receptor medium for 24 h. The permeation studies of the active components demonstrated a good correlation (r² = 0.9136) of P_app values between the drugs' permeation through the PVPA_SC model and porcine ear skin.

Conclusion: Keratin contained composite phospholipid vesicle-based permeation assay models have been proven to be potential skin tools in topical/transdermal permeation studies.

Objective: The study was aimed at formulating temozolomide (TMZ) loaded gelatin nanoparticles (GNPs) encapsulated into polyvinyl alcohol (PVA) nanofibers (TMZ-GNPs-PVA NFs) as the nano-in-nanofiber delivery system. The secondary objective was to explore the sustained releasing ability of this system and to assess its enhanced cellular uptake against U87MG glioma cells in vitro.

Significance: Nano-in-nanofibers are the emerging drug delivery systems for treating a wide range of diseases including cancers as they overcome the challenges experienced by nanoparticles and nanofibers alone.

Methods: The drug-loaded GNPs were formulated by one-step desolvation method. The Design of Experiments (DoE) was used to optimize nanoparticle size and entrapment efficiency. The optimized drug-loaded nanoparticles were then encapsulated within nanofibers using blend electrospinning technique. The U87MG glioma cells were used to investigate the uptake of the formulation.

Results: A 3² factorial design was used to optimize the mean particle size (145.7 nm) and entrapment efficiency (87.6%) of the TMZ-loaded GNPs which were subsequently ingrained into PVA nanofibers by electrospinning technique. The delivery system achieved a sustained drug release for up to seven days (in vitro). The SEM results ensured that the expected nano-in-nanofiber delivery system was achieved. The uptake of TMZ-GNPs-PVA NFs by cells was increased by a factor of 1.964 compared to that of the pure drug.

Conclusion: The nano-in-nanofiber drug delivery system is a potentially useful therapeutic strategy for the management of glioblastoma multiforme.

Objective: Magnolol (MG) and Brucea javanica (L.) Merr. oil (BJO) possess synergetic anti-tumor effects, but have poor water solubility and stability, which results in low oral bioavailability.

Significance: The MG loaded self-microemulsion drug delivery system (MG-SMDDS) with BJO as oil phase component was utilized to improve the cellular uptake and synergetic anti-tumor effects.

Methods: Compatibility study and pseudoternary phase diagram (PTPD) were respectively employed to screen for the composition and proportion of oil phase in the formulation. Central composite design-effect surface method was applied to optimize proportion of each formulation condition. The droplet size, ζ-potential, colloid stability, encapsulation rate (ER) and in vitro dissolution rate of MG-SMDDS were evaluated. Furthermore, cellular uptake and cytotoxicity of the microemulsion on HepG2 cells were assessed.

Results: The optimal composition of MG-SMDDS was: MG (9.09%), castor oil (7.40%), BJO (2.47%), Cremophor EL 35 (54.04%) and 1, 2-propanediol (27.01%). The MG-SMDDS exhibited satisfactory droplet size, ζ-potential, colloid stability and ER, as well as faster dissolution rate than free MG. More importantly, SMEDDS containing BJO could enhance the cellular uptake and cytotoxicity of free BJO and free MG on tumor cells.

Conclusions: The BJO self-microemulsion delivery technique can provide an idea for design of oral delivery vehicles based on BJO.

Objective: The purpose of this research was to determine any connections between the characteristics of oleogels made of beeswax and the impact of mango butter.

Methods: Oleogel was prepared through inverted tube methods, and optimized through oil binding capacity. Other evaluations like bright field and polarized microscopy, Fourier-transform infrared (FTIR) spectroscopy, crystallization kinetics, mechanical study, and X-ray diffractometry (XRD). The drug release kinetic studies and in vitro antibacterial studies were performed.

Results: FTIR study reveals that the gelation process does not significantly alter the chemical composition of the individual components. Prepared gel exhibiting fluid-like behavior or composed of brittle networks is particularly vulnerable to disruptions in their network design. The incorporation of mango butter increases the drug permeation. In-vitro microbial efficacy study was found to be excellent.

Conclusion: The studies revealed that mango butter can be used to modify the physico-chemical properties of the oleogels.