Design-of-Experiment-Assisted Fabrication of Biodegradable Polymeric Nanoparticles: In Vitro Characterization, Biological Activity, and In Vivo Assessment.

Berberine (BER) is an alkaloid obtained from berberis plant having broad biological activities including anticancer. BER-encapsulated alginate (ALG)/chitosan (CHS) nanoparticles (BER-ALG/CHS-NPs) were developed for long-acting improved treatment in breast cancer. The surface of the NPs was activated by a conjugation reaction, and thereafter, the BER-ALG/CHS-NP surface was grafted with folic acid (BER-ALG/CHS-NPs-F) for specific targeting in breast cancer. BER-ALG/CHS-NPs-F was optimized by applying the Box-Behnken design using Expert design software. Moreover, formulations are extensively evaluated in vitro for biopharmaceutical performances and tested for cell viability, cellular uptake, and antioxidant activity. The comparative pharmacokinetic study of formulation and free BER was carried out in animals for estimation of bioavailability. The particle size recorded for the diluted sample using a Malvern Zetasizer was 240 ± 5.6 nm. The ζ-potential and the predicted % entrapment efficiency versus (vs) observed were +18 mV and 83.25 ± 2.3% vs 85 ± 3.5%. The high % drug release from the NPs was recorded. The analytical studies executed using infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction expressed safe combinations of the components in the formulation and physical state of the drug revealed to be amorphous in the formulation. Cytotoxicity testing demonstrated that the formulation effectively lowered the cell viability and IC50 of the tested cell line in comparison to a raw drug. The cellular uptake of BER-ALG/CHS-NPs-F was 5.5-fold higher than that of BER-suspension. The antioxidant capacities of BER-ALG/CHS-NPs-F vs BER-suspension by the DPPH assay were measured to be 62.3 ± 2.5% vs 30 ± 6%, indicating good radical scavenging power of folate-conjugated NPs. The developed formulation showed a 4.4-fold improved oral bioavailability compared to BER-suspension. The hemolytic assay intimated <2% destruction of erythrocytes by the developed formulation. The observed experimental characterization results such as cytotoxicity, cellular uptake, antioxidant activity, and improved absorption suggested the effectiveness of BER-ALG/CHS-NPs-F toward breast cancer.

Preparation, Characterization, and Evaluation of Curcumin-Graphene Oxide Complex-Loaded Liposomes against Staphylococcus aureus in Topical Disease.

This study describes the development and characterization of curcumin with graphene oxide complex (CUR + GO) loaded into liposomes for treating skin disease. The developed complex was characterized by X-ray diffraction and showed a broad halo pattern, confirming the amorphous nature of the resulting complex. Furthermore, scanning electron microscopy revealed the irregular porous morphology of the complex-highlighting loss of the crystallinity and the emergence of the amorphous phase. Additionally, the liposomes showed long-term stability at 2-8 °C and 25 ± 2 °C/60 ± 5%RH with nonsignificant variations in the particle size, polydispersity index, and zeta potential. Overall, optical and high-resolution transmission electron microscopy images of liposomes showed a consistent shape, and no aggregation with uniform particle size distribution was observed. Furthermore, the cumulative drug release in the first 6 h was 71.24 and 64.24% for CUR-loaded liposomes and CUR-GO-loaded liposomes, respectively. The lower value of drug release might be attributed to the complex development. The drug release model found the first order with non-Fickian diffusion process, which is often observed at higher n > 0.5. The antibacterial activity of the CUR with GO-loaded liposome (D2) offered higher anti-microbial activity over other formulations against the mentioned bacterial microorganism that causes skin diseases.

Analysis of Anti-Arrhythmic Impacts of Crocin through Estimation of Expression of Cx43 in Myocardial Infarction Using a Rat Animal Model.

Arrhythmia is an important cause of death after myocardial infarction (MI). Different substances have been evaluated for their anti-arrhythmic effect in MI. This study was performed to evaluate the anti-arrhythmic impacts of crocin in an MI animal model (rat) by estimation of the expression of connexin 43 (Cx43). Fifty male Sprague-Dawley rats were grouped into 5 groups, each composed of 10 rats. The first group was regarded as the normal control group and the second one was considered as the MI group, which was caused by ligation of the left anterior descending artery. The other three groups received crocin 50 or 10 mg/kg/day or metoprolol 100 mg/kg/day for 1 week, following ligation of the left anterior descending artery. Evaluated outcomes were cardiac Cx43 expression, arrhythmia incidence, histological findings, and myocyte resting potential. Crocin-treated MI groups showed a significantly lower arrhythmia score than the non-treated MI group, 10 mg/kg/day (1.85 ± 0.55, p < 0.01) and 50 mg/kg/day (1.70 ± 0.33, p < 0.01). Groups that received crocin 10 mg/kg/day (66.30 ± 2.59, p < 0.01), crocin 50 mg/kg/day (68.10 ± 2.43, p < 0.01), and metoprolol 100 mg/kg/day (-63.54 ± 0.63 mV, p < 0.01) significantly prevented depolarization in comparison with the non-treated MI group. Expression of Cx43 mRNA in crocin 10 mg/kg/day (1.54 ± 0.24, p < 0.01), crocin 50 mg/kg/day (1.73 ± 0.09, p < 0.01), and metoprolol 100 mg/kg/day (1.75 ± 0.14, p < 0.01) treatment groups was significantly higher in comparison with the non-treated MI group. Crocin showed a preventive effect on the arrhythmogenic impact of MI in an experimental model of ischemic injury through an increase in expression of Cx43.