In silico design and mechanistic study of niosome-encapsulated curcumin against multidrug-resistant Staphylococcus aureus biofilms.

Curcumin, an important natural component of turmeric, has been known for a long time for its antimicrobial properties. This study aimed to investigate the anti-biofilm action of the niosome-encapsulated curcumin and explore the involved anti-biofilm mechanism. In silico investigations of ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) were first performed to predict the suitability of curcumin for pharmaceutical application. Curcumin showed low toxicity but at the same time, low solubility and low stability, which, in turn, might reduce its antimicrobial activity. To overcome these intrinsic limitations, curcumin was encapsulated using a biocompatible niosome system, and an encapsulation efficiency of 97% was achieved. The synthesized curcumin-containing niosomes had a spherical morphology with an average diameter of 178 nm. The niosomal curcumin was capable of reducing multi-drug resistant (MDR) Staphylococcus aureus biofilm 2-4-fold compared with the free curcumin. The encapsulated curcumin also demonstrated no significant cytotoxicity on the human foreskin fibroblasts. To understand the interaction between curcumin and S. aureus biofilm, several biofilm-related genes were analyzed for their expression. N-acetylglucosaminyl transferase (IcaD), a protein involved in the production of polysaccharide intercellular adhesion and known to play a function in biofilm development, was found to be downregulated by niosomal curcumin and showed high binding affinity (-8.3 kcal/mol) with curcumin based on molecular docking analysis. Our study suggests that the niosome-encapsulated curcumin is a promising approach for the treatment of MDR S. aureus biofilm and can be extended to biofilms caused by other pathogens.

In silico and in vitro studies of GENT-EDTA encapsulated niosomes: A novel approach to enhance the antibacterial activity and biofilm inhibition in drug-resistant Klebsiella pneumoniae.

Klebsiella pneumoniae (Kp) is a common pathogen inducing catheter-related biofilm infections. Developing effective therapy to overcome antimicrobial resistance (AMR) in Kp is a severe therapeutic challenge that must be solved. This study aimed to prepare niosome-encapsulated GENT (Gentamicin) and EDTA (Ethylenediaminetetraacetic acid) (GENT-EDTA/Nio) to evaluate its efficacy toward Kp strains. The thin-film hydration method was used to prepare various formulations of GENT-EDTA/Nio. Formulations were characterized for their physicochemical characteristics. GENT-EDTA/Nio properties were used for optimization with Design-Expert Software. Molecular docking was utilized to determine the antibacterial activity of GENT. The niosomes displayed a controlled drug release and storage stability of at least 60 days at 4 and 25 °C. GENT-EDTA/Nio performance as antimicrobial agents has been evaluated by employing agar well diffusion method, minimum bactericidal concentration (MBC), and minimum inhibitory concentration (MIC) against the Kp bacteria strains. Biofilm formation was investigated after GENT-EDTA/Nio administration through different detection methods, which showed that this formulation reduces biofilm formation. The effect of GENT-EDTA/Nio on the expression of biofilm-related genes (mrkA, ompA, and vzm) was estimated using QRT-PCR. MTT assay was used to evaluate the toxicity effect of niosomal formulations on HFF cells. The present study results indicate that GENT-EDTA/Nio decreases Kp's resistance to antibiotics and increases its antibiotic and anti-biofilm activity and could be helpful as a new approach for drug delivery.

Folate-Targeted Curcumin-Loaded Niosomes for Site-Specific Delivery in Breast Cancer Treatment: In Silico and In Vitro Study.

As the most common cancer in women, efforts have been made to develop novel nanomedicine-based therapeutics for breast cancer. In the present study, the in silico curcumin (Cur) properties were investigated, and we found some important drawbacks of Cur. To enhance cancer therapeutics of Cur, three different nonionic surfactants (span 20, 60, and 80) were used to prepare various Cur-loaded niosomes (Nio-Cur). Then, fabricated Nio-Cur were decorated with folic acid (FA) and polyethylene glycol (PEG) for breast cancer suppression. For PEG-FA@Nio-Cur, the gene expression levels of Bax and p53 were higher compared to free drug and Nio-Cur. With PEG-FA-decorated Nio-Cur, levels of Bcl2 were lower than the free drug and Nio-Cur. When MCF7 and 4T1 cell uptake tests of PEG-FA@Nio-Cur and Nio-Cur were investigated, the results showed that the PEG-FA-modified niosomes exhibited the most preponderant endocytosis. In vitro experiments demonstrate that PEG-FA@Nio-Cur is a promising strategy for the delivery of Cur in breast cancer therapy. Breast cancer cells absorbed the prepared nanoformulations and exhibited sustained drug release characteristics.

Review of Bioprinting in Regenerative Medicine: Naturally Derived Bioinks and Stem Cells.

Regenerative medicine offers the potential to repair or substitute defective tissues by constructing active tissues to address the scarcity and demands for transplantation. The method of forming 3D constructs made up of biomaterials, cells, and biomolecules is called bioprinting. Bioprinting of stem cells provides the ability to reliably recreate tissues, organs, and microenvironments to be used in regenerative medicine. 3D bioprinting is a technique that uses several biomaterials and cells to tailor a structure with clinically relevant geometries and sizes. This technique's promise is demonstrated by 3D bioprinted tissues, including skin, bone, cartilage, and cardiovascular, corneal, hepatic, and adipose tissues. Several bioprinting methods have been combined with stem cells to effectively produce tissue models, including adult stem cells, embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and differentiation techniques. In this review, technological challenges of printed stem cells using prevalent naturally derived bioinks (e.g., carbohydrate polymers and protein-based polymers, peptides, and decellularized extracellular matrix), recent advancements, leading companies, and clinical trials in the field of 3D bioprinting are delineated.