Drug Development and Industrial Pharmacy最新文献

Objective: The purpose of this study was to prepare and evaluate chitosan (CS) gel containing metformin hydrochloride (MET)-loaded polycaprolactone (PCL) nanoparticles (NPs) for topical treatment of melanoma.

Significance: Topical administration of MET-PCL NPs-CS gel improves penetration of drug, decreases side effects, and increases efficacy of treatment.

Methods: MET-PCL NPs were prepared by double emulsion method. Particle size, charge, encapsulation efficiency (EE), release, and morphology were evaluated. MET-PCL NPs-CS gel formulation was characterized in terms of organoleptic properties, pH, gelling time, viscosity, spreadability, release, and morphology. Cytotoxicity was performed on B16F10 cells. Ex vivo permeability was done with pig skin.

Results: The size, charge, and EE were found to be 180 ± 10 nm, -11.4 mV, and 93%. SEM images showed that NPs were spherical and smooth. An initial burst release followed by a slower release was observed. MET-PCL NPs-CS gel was found to be transparent. The pH was 4.9 ± 0.05. The gelation time was 1.6 ± 0.2 min. The viscosity results confirm pseudoplastic behavior of gel. The spreadability by % area was 392 ± 6.4 cm. The images showed that gelling network of CS gel was composed of suspended NPs. The viscosity was between 554 and 3503 cP. MET-PCL NPs-CS gel showed prolonged release up to 72 h. On B16F10 cells, gel showed higher cytotoxicity compared to MET solution. MET-PCL NPs-CS gel had twofold higher permeability in pig skin compared with MET-CS gel.

Conclusion: Topical administration of MET-PCL NPs-CS gel into the skin resulted in improved dermal penetration and this promising approach may be of value in effective treatment of melanoma and other skin cancers.

Objective: This study was aimed to develop a cationic lipoplex formulation loaded with Nintedanib and miR-29b (LP-NIN-miR) as an alternative approach in the combination therapy of idiopathic pulmonary dibrosis (IPF) by proving its additive anti-fibrotic therapeutic effects through in vitro lung fibrosis model.

Significance: This is the first research article reported that the LP-NIN-MIR formulations in the treatment of IPF.

Methods: To optimize cationic liposomes (LPs), quality by design (QbD) approach was carried out. Optimized blank LP formulation was prepared with DOTAP, CHOL, DOPE, and DSPE-mPEG 2000 at the molar ratio of 10:10:1:1. Nintedanib loaded LP (LPs-NIN) were produced by microfluidization method and were incubated with miR-29b at room temperature for 30 min to obtain LP-NIN-miR. To evaluate the cellular uptake of LP-NIN-miR, NIH/3T3 cells were treated with 20 ng.mL^-1 transforming growth factor-β1 (TGF-β1) for 96 h to establish the in vitro IPF model and incubated with LP-NIN-miR for 48 h.

Results: The hydrodynamic diameter, polydispersity index (PDI), and zeta potential of the LP-NIN-miR were 87.3 ± 0.9 nm, 0.184 ± 0.003, and +24 ± 1 mV, respectively. The encapsulation efficiencies of Nintedanib and miR-29b were 99.8% ± 0.08% and 99.7% ± 1.2%, respectively. The results of the cytotoxicity study conducted with NIH/3T3 cells indicated that LP-NIN-miR is a safe delivery system.

Conclusions: The outcome of the transfection study proved the additive anti-fibrotic therapeutic effect of LP-NIN-miR and suggested that lipoplexes are effective delivery systems for drug and nucleic acid to the NIH/3T3 cells in the treatment of IPF.

Objective: The current review is designed to elaborate and reveal the underlying mechanism of sericin and its conjugates of drug delivery during wounds and wound-related issues.

Significance: Wound healing is a combination of different humoral, molecular, and cellular mechanisms. Various natural products exhibit potential in wound healing but among them, sericin, catches much attention of researchers due to its bio-functional properties such as being biodegradable, biocompatible, anti-oxidant, anti-bacterial, photo-protector, anti-inflammatory and moisturizing agent.

Methods and results: Sericin triggers the activity of anti-inflammatory cytokines which decrease cell adhesion and promote epithelial cell formation. Moreover, sericin enhances the anti-oxidant enzymes in the wounded area which scavenge the toxic consequences of reactive species (ROS).

Conclusions: This article highlights the mechanisms of how topical administration of sericin formulations along with 4-hexylresorcinol,ChitosanAg@MOF-GO, polyvinyl alcohol (PVA), platelet lysate and UV photo cross-linked hydrogel sericin methacrylate which recruits a large number of cytokines on wounded area that stimulate fibroblasts and keratinocyte production as well as collagen deposition that led to early wound contraction. It also reviews the different sericin-based nanoparticles that play a significant role in rapid wound healing.

Background: Obesity has become a prevalent issue worldwide, leading to various complications such as hyperlipidemia, diabetes, and cardiovascular problems. Statins, as FDA approved anti-hyperlipidemic drugs, still pose some concerns upon their administration. Recently, researchers have looked for natural products as an alternative to manage hyperlipidemia and obesity.

Aim: This work aimed to study the hypolipidemic effect of Lepidium sativum garden cress (GC) from different preparations; orally administered seeds, and hydrogel, in comparison to atorvastatin.

Methods: GC hydrogel was prepared from the GC aqueous extract and pharmaceutically evaluated for its pH, spreadability, seeds content, homogeneity, rheology, and in vitro release. The rat's body weight, blood glucose levels, total lipid profile, and liver biomarkers were evaluated on obese rats for one month. In addition, the histopathology study was also performed.

Results: GC hydrogel had acceptable pharmaceutical properties and showed a sustained release performance over 24 h. Oral and topical GC significantly reduced the lipid profiles, blood sugar and ALT, AST levels more than the negative control group and comparable to atorvastatin. It was found that oral GC showed a significant effect on the percentage decrease in the rat's body weight than the applied hydrogel. Histopathology study revealed a better outcome in the histological structure of pancreas and liver compared with rats feed on high fat diet post-treatment for one month.

Conclusion: GC orally administered, or topically applied hydrogel could be a promising, safe alternative formulation to atorvastatin in managing hyperlipidemia and normalizing body weight of obese rats.

Objectives: In this research paper, an investigation has been made to assess the simultaneous effect of a solubility enhancement approach, i.e., hydrotropy on the solubility and apparent permeability of piroxicam. The solubility of piroxicam (PRX) a BCS (biopharmaceutics classification system) class II drug has been increased using a mixed hydrotropy approach. This study is based on identifying the pattern of solubility-permeability interplay and confirming whether every solubility gain results in a concomitant decrease in permeability or permeability remains unaffected.

Method: Solid dispersions of PRX were formulated using two hydrotropes, viz., sodium benzoate (SB) and piperazine (PP) by solvent evaporation method. A comprehensive 3²factorial design was employed to study the effect of hydrotropes on the solubility and permeability of PRX. Subsequently, PRX tablets containing these solid dispersions were formulated and evaluated.

Key findings: SB and PP displayed a significant increase in the solubility of PRX ranging from 0.99 to 2.21 mg/mL for F1-F9 batches attributed to the synergistic effect of hydrotropes. However, there is a reduction in PRX permeability with increasing hydrotrope levels. The decline in permeability was notably less pronounced compared to the simultaneous rise in aqueous solubility of PRX.

Conclusion: An evident tradeoff between permeability and solubility emerged through the mixed hydrotropic solubilization for PRX. As PRX has generally higher intrinsic permeability, it has been assumed that this permeability loss will not affect the overall absorption of PRX. However, it may affect the absorption of drugs with limited permeability. Therefore, solubility permeability interplay should be investigated during solubility enhancement.

Objective: The purpose of this study is to investigate the taste masking of Paracetamol granules in the range of 250-850 µm, coated by two nanocomposites prepared from Eudragit^® E100, nanozinc oxide, and nanochitosan, respectively, from 1 to 5% by the weight of the granules.

Methods: In this study, Paracetamol granules were coated in several formulas with two different types of nanocomposites (polymeric and mineral) on two sizes of granules to reduce bitter taste and with the FBC method and pH-sensitive polymers (Eudragit^® E100).

Results: The effect of nanoparticles (Nano zinc oxide and Nanochitosan) on taste-masking Paracetamol was studied with dissolution-coated granules in vitro by simulating in the oral (pH 6.8) range. Based on the results of the studies, the rate of drug release was confirmed by the taste test, and the formulated granule with 5% nano-chitosan (F14) had the best bitter taste mask function of all samples. These results were also confirmed by scanning electron microscopy (SEM) analysis, which showed a smoother and more stable surface than the samples obtained from other formulations.

Conclusion: In the comparison of the release of two types of nanocomposites in the dissolution test, it was shown that the type B granules of Paracetamol's 5% nano-chitosan-coated granule (F14) were released 99% less than Paracetamol's 5% nano-ZnO-coated granule (F11). and Paracetamol's 1% nano-chitosan-coated granule (F12) was released 91% less than Paracetamol's 1% nano-ZnO-coated granule (F9). The results showed that nano-chitosan-coated granules have better coverage of bitter taste instead of nano-ZnO.

Objective and significance: Reducing the dimensions, when other additives are present, shows potential as a method to improve the dissolution and solubility of biopharmaceutical classification system class II drugs that have poor solubility. In this investigation, the process involved grinding naproxen with nicotinamide with the aim of improving solubility and the rate of dissolution.

Methods: Naproxen was subjected to co-milling with urea, dimethylurea, and nicotinamide using a planetary ball mill for a duration of 90 min, maintaining a 1:1 molar ratio for the excipients (screening studies). The co-milled combinations, naproxen in its pure milled form, and a physical mixture were subjected to analysis using X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), and solubility assessment. The mixture displaying the highest solubility (naproxen-nicotinamide) was chosen for further investigation, involving testing for intrinsic dissolution rate (IDR) and Fourier-transform infrared spectroscopy (FTIR) after co-milling for both 90 and 480 min.

Results and conclusion: The co-milled combination, denoted as S-3b and consisting of the most substantial ratio of nicotinamide to naproxen at 1:3, subjected to 480 min of milling, exhibited a remarkable 45-fold increase in solubility and a 9-fold increase in IDR. XRPD analysis of the co-milled samples demonstrated no amorphization, while SEM images portrayed the aggregates of naproxen with nicotinamide. FTIR outcomes negate the presence of any chemical interactions between the components. The co-milled sample exhibiting the highest solubility and IDR was used to create a tablet, which was then subjected to comprehensive evaluation for standard attributes. The results revealed improved compressibility and dissolution properties.

Objectives: Melanin is considered the main chromophore for laser hair removal. Due to a lack of laser-absorbing chromophores, removing non-pigmented hair with laser is quite problematic with unsatisfactory outcomes. This problem could be solved by delivering more melanin to the area around the hair follicle and enhancing that area as a target for light absorption. The insolubility of Sepia melanin as an exogenous dye, in most solvents, limits its bioavailability and thus its clinical use.

Methods: In our study, to overcome the solubility problems and increase the bioavailability of melanin for biomedical and cosmetic applications, natural sepia melanin was loaded in different nano-delivery systems (spanlastics and transfersomes) to be delivered to the hair follicles. The different formulations of melanin were prepared and characterized. In vivo skin deposition and histopathological studies were conducted on albino mice.

Results: Transmission electron microscopy (TEM) showed the spherical shape of the prepared vesicles with an average particle size of 252 and 262 nm and zeta potential of -22.5 and -35 mV for melanin spanlastics and melanin transfersomes, respectively. Histopathological examination of hair follicles and pilosebaceous glands for the irradiated and non-irradiated albino mice skin was studied post the application of the prepared formulations topically and subcutaneously. Qualitative statistical analysis was conducted and melanin transfersomes and melanin spanlastics showed significant damage to pilosebaceous glands and hair follicles with a p-value of 0.031 and 0.009 respectively.

Conclusion: Melanin nanovesicles as transfersomes and spanlastics could be considered a promising approach for the removal of non-pigmented hair.

The objective of the study was to create a reliable method that could be used to evaluate the particle size distribution of samples and pre-mixes in real-world situations, particularly those consisting of typical formulation blends. The goal was to use this method to assess the uniformity of the samples and ensure that they met the required quality standards. The researchers aimed to create a method that could be easily incorporated into the manufacturing process, providing a practical and efficient solution. This study demonstrates the use of ImageJ software to analyze the particle size distribution (PSD) of powders. The technique produces qualitative data from microscopy images and quantitative data from analysis of parameters including average diameter, D₁₀, D₅₀, D₉₀, and standard deviation. The method was tested with various treatments, showing differentiating outcomes in all cases. The alternate technique provides a rapid and cost-effective method for PSD analysis, surpassing the limitations of sieve analysis. Extensive testing of the method, using a variety of sample types, including typical formulation blends, was performed. The results suggest that the method can effectively assess the morphology of changing materials during batch manufacturing and characterize uniformity in blends. The methodology has the capability to identify attributes related to PSD that are typically required to be monitored during manufacturing. The technique allows for accurate and reliable quantification of the attributes through image capture technology. The technique has future potential and has important implications for material science, powder rheology, pharmaceutical formulation development, and continual process monitoring.

Introduction: Breast cancer (BC) is the most common malignancy in women globally. Significant progress has been made in developing structural nanoparticles (NPs) and formulations for targeted smart drug delivery (SDD) of pharmaceuticals, improving the precision of tumor cell targeting in therapy.

Significance: Magnetic hyperthermia (MHT) treatment using magneto-liposomes (MLs) has emerged as a promising adjuvant cancer therapy.

Methods: CoFe₂O₄ magnetic NPs (MNPs) were conjugated with nanoliposomes to form MLs, and the anticancer drug quercetin (Que) was loaded into MLs, forming Que-MLs composites for antitumor approach. The aim was to prepare Que-MLs for DD systems (DDS) under an alternating magnetic field (AMF), termed chemotherapy/hyperthermia (chemo-HT) techniques. The encapsulation efficiency (EE), drug loading capacity (DL), and drug release (DR) of Que and Que-MLs were evaluated.

Results: The results confirmed successful Que-loading on the surface of MLs, with an average diameter of 38 nm and efficient encapsulation into MLs (69%). In vitro, experimental results on MCF-7 breast cells using MHT showed high cytotoxic effects of novel Que-MLs on MCF-7 cells. Various analyses, including cytotoxicity, apoptosis, cell migration, western blotting, fluorescence imaging, and cell membrane internalization, were conducted. The Acridine Orange-ethidium bromide double fluorescence test identified 35% early and 55% late apoptosis resulting from Que-MLs under the chemo-HT group. TEM results indicated MCF-7 cell membrane internalization and digestion of Que-MLs, suggesting the presence of early endosome-like vesicles on the cytoplasmic periphery.

Conclusions: Que-MLs exhibited multi-modal chemo-HT effects, displaying high toxicity against MCF-7 BC cells and showing promise as a potent cytotoxic agent for BC chemotherapy.