Tyrosol-gold nanoparticle functionalized acacia gum-PVA nanofibers for mitigation of Candida biofilm.

Increasing incidences of fungal infections and prevailing antifungal resistance in healthcare settings has given rise to an antifungal crisis on a global scale. The members of the genus Candida, owing to their ability to acquire sessile growth, are primarily associated with superficial to invasive fungal infections, including the implant-associated infections. The present study introduces a novel approach to combat the sessile/biofilm growth of Candida by fabricating nanofibers using a nanoencapsulation approach. This technique involves the synthesis of tyrosol (TYS) functionalized chitosan gold nanocomposite, which is then encapsulated into PVA/AG polymeric matrix using electrospinning. The FESEM, FTIR analysis of prepared TYS-AuNP@PVA/AG NF suggested the successful encapsulation of TYS into the nanofibers. Further, the sustained and long-term stability of TYS in the medium was confirmed by drug release and storage stability studies. The prepared nanomats can absorb the fluid, as evidenced by the swelling index of the nanofibers. The growth and biofilm inhibition, as well as the disintegration studies against Candida, showed 60-70 % biofilm disintegration when 10 mg of TYS-AuNP@PVA/AG NF was used, hence confirming its biological effectiveness. Subsequently, the nanofibers considerably reduced the hydrophobicity index and ergosterol content of the treated cells. Considering the challenges associated with the inhibition/disruption of fungal biofilm, the fabricated nanofibers prove their effectiveness against Candida biofilm. Therefore, nanocomposite-loaded nanofibers have emerged as potential materials that can control fungal colonization and could also promote healing.

Cinnamaldehyde incorporated gellan/PVA electrospun nanofibers for eradicating Candida biofilm.

Immunocompromised patients encounter fungal infections more frequently than healthy individuals. Conventional drugs associated health risk and resistance, portrayed fungal infections as a global health problem. This issue needs to be answered immediately by designing a novel anti-fungal therapeutic agent. Phytoactive molecules based therapeutics are most suitable candidate due to their low cytotoxicity and minimal side effects to the host. In this study, cinnamaldehyde (CA), an FDA approved phytoactive molecule present in cinnamon essential oil was incorporated into gellan (GA)/poly vinyl alcohol (PVA) based electrospun nanofibers to resolve the issues like low water solubility, high volatility and irritant effect associated with CA and also to enhance its therapeutic applications. The drug encapsulation, morphology and physical properties of the synthesized CA nanofibers were evaluated by FESEM, AFM, TGA, FTIR and static water contact angle analysis. The average diameters of CA encapsulated GA/PVA nanofibers and GA/PVA nanofibers were recorded to be 278.5 ± 57.8 nm and 204.03 ± 39.14 nm, respectively. These nanofibers were evaluated for their anti-biofilm activity against Candida using XTT (2, 3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)-carbonyl]-2H-tetrazolium salt) reduction assay. Data demonstrated that CA encapsulated GA/PVA nanofibers can effectively eradicate 89.29% and 50.45% of Candida glabrata and Candida albicans biofilm respectively. CA encapsulated nanofibers exhibited brilliant antimicrobial property against Staphylococcus aureus and Pseudomonas aeruginosa. The cytotoxicity assay demonstrated that nanofibers loaded with CA have anticancer properties as it reduces cell viability of breast cancer cells (MCF-7) by 27.7%. These CA loaded GA/PVA (CA-GA/PVA) nanofibers could be used as novel wound dressing material and coatings on biomedical implants to eradicate biofilm.

Eugenol-acacia gum-based bifunctional nanofibers as a potent antifungal transdermal substitute.

Aim: Fungal biofilms interfere with the wound healing processes. Henceforth, the study aims to fabricate a biomaterial-based nano-scaffold with the dual functionalities of wound healing and antibiofilm activity. Methods: Nanofibers comprising acacia gum, polyvinyl alcohol and inclusion complex of eugenol in ß-cyclodextrin (EG-NF) were synthesized using electrospinning. Antibiofilm studies were performed on Candida species, and the wound-healing activity was evaluated through an in vivo excision wound rat model. Results: The EG-NF potentially eradicated the mature biofilm of Candida species and their clinical isolates. Further, EG-NF also enhanced the re-epithelization and speed of wound healing in in vivo rat experiments. Conclusion: The study established the bifunctional applications of eugenol nanofibers as a transdermal substitute with antifungal potency.

Eucalyptol/ ß-cyclodextrin inclusion complex loaded gellan/PVA nanofibers as antifungal drug delivery system.

Fungal infections pose a serious threat to humankind due to the toxicity of conventional antifungal therapy and continuous emerging incidence of multidrug resistance. Essential oils fascinated researchers because of their broad antimicrobial activity and minimal cytotoxicity. However, hydrophobic, volatile and low water solubility of essential oils hinder their applications in pharmaceutical industries. Therefore, in this study we have loaded eucalyptol/ ß-cyclodextrin inclusion complex to gellan/polyvinyl alcohol nanofibers (EPNF) to eradicate Candida albicans and Candida glabrata biofilms. The electrospun nanofibers characterized by various physicochemical techniques and it was observed that EPNF possess highly hydrophilic surface property that facilitate rapid drug release. EPNF inhibited approximately 70% biofilm of C. albicans and C. glabrata. Time kill results depicted that eucalyptol (EPTL) encapsulation in the nanofibers prolonged its antifungal activity than the pure EPTL. Electron microscopy studies revealed that EPNF disrupted the cell surface of Candida. Collectively the current study suggested nanofiber encapsulation enhanced antibiofilm activity of eucalyptol and these nanoscale systems can serve as an alternative therapeutic strategy to treat fungal infections. Further, the developed nanofibrous materials can be applied as cost effective coating agent for biomedical implants.

Delivery of dual miRNA through CD44-targeted mesoporous silica nanoparticles for enhanced and effective triple-negative breast cancer therapy.

The development of new therapeutic strategies to target triple-negative breast cancer (TNBC) is in much demand to overcome the roadblocks associated with the existing treatment procedures. In this regard, therapies targeting the CD44 receptor have drawn attention for more than a decade. MicroRNAs (miRNAs) modulate post-transcriptional gene regulation and thus, the correction of specific miRNA alterations using miRNA mimics or antagomiRs is an emerging strategy to normalize the genetic regulation in the tumor microenvironment. It has been acknowledged that miR-34a is downregulated and miR-10b is upregulated in TNBC, which promotes tumorigenesis and metastatic dissemination. However, there are a few barriers related to miRNA delivery. Herein, we have introduced tailored mesoporous silica nanoparticles (MSNs) for the co-delivery of miR-34a-mimic and antisense-miR-10b. MSN was functionalized with a cationic basic side chain and then loaded with the dual combination to overexpress miR-34a and downregulate miR-10b simultaneously. Finally, the loaded MSNs were coated with an hyaluronic acid-appended PEG-PLGA polymer for specific targeting. The cellular uptake, release profile, and subsequent effect in TNBC cells were evaluated. In vitro and in vivo studies demonstrated high specificity in TNBC tumor targeting, leading to efficient tumor growth inhibition as well as the retardation of metastasis, which affirmed the clinical application potential of the system.

Delivery of thymoquinone through hyaluronic acid-decorated mixed Pluronic® nanoparticles to attenuate angiogenesis and metastasis of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly aggressive and metastatic subtype of breast cancer showing non-responsiveness to most available therapeutic options. Therefore, smart therapeutic approaches to selectively transport and target TNBCs are required. Herein, we developed thymoquinone (TQ)-loaded, hyaluronic acid (HA)-conjugated Pluronic® P123 and F127 copolymer nanoparticles (HA-TQ-Nps) as a selective drug-carrying vehicle to deliver anticancer phytochemical TQ to TNBC cells. The mean size of nanoparticles was around 19.3 ± 3.2 nm. and they were stable at room temperature up to 4 months. HA-TQ-Nps were immensely cytotoxic towards TNBC cells but did not show the toxic effect on normal cells. Detailed investigations also demonstrated its pro-apoptotic, anti-metastatic and anti-angiogenic activity. In-depth mechanistic studies highlighted that HA-TQ-Nps retarded cell migration of TNBC cells through up-regulation of microRNA-361 which in turn down-regulated Rac1 and RhoA mediated cell migration and also perturbed the cancer cell migration under the influence of the autocrine effect of VEGF-A. Moreover, HA-TQ-Np-treatment also perturbed tumor-induced vascularization by reducing the secretion of VEGF-A. The anti-metastatic and anti-angiogenic activity of HA-TQ-Nps was found to be evident in both MDA-MB-231 xenograft chick embryos and 4T1-mammary solid tumor model in syngeneic mice. Thus, an innovative targeted nano-therapeutic approach is being established to reduce the tumor burden and inhibit metastasis and angiogenesis simultaneously for better management of TNBC.

Transferrin-decorated thymoquinone-loaded PEG-PLGA nanoparticles exhibit anticarcinogenic effect in non-small cell lung carcinoma via the modulation of miR-34a and miR-16.

Non-small cell lung carcinoma (NSCLC) is a highly lethal type of cancer with limited therapeutic avenues available to date. In the present study, we formulated PEGylated PLGA thymoquinone nanoparticles (TQ-Np) for improved TQ delivery to NSCLC cells. Transferrin (TF), a biodegradable, non-immunogenic and non-toxic protein, is well known to bind to TFR (transferrin receptor) over-expressed in non-small cell lung carcinoma A549 cells. Thus, the further decoration of the PEGylated PLGA thymoquinone nanoparticles with transferrin (TF-TQ-Np) enhanced the internalization of the nanoparticles within the A549 cells and the activity of TQ. We established TF-TQ-Np as a potent anti-tumorigenic agent through the involvement of p53 and the ROS feedback loop in regulating the microRNA (miRNA) circuitry to control apoptosis and migration of NSCLC cells. TF-TQ-Np-mediated p53 up-regulation favored the potential simultaneous activation of miR-34a and miR-16 targeting Bcl2 to induce apoptosis in the A549 cells. Additionally, TF-TQ-Np also restricted the migration through actin de-polymerization via activation of the p53/miR-34a axis. Further studies in chick CAM xenograft models confirmed the anti-cancer activity of TF-TQ-Np by controlling the p53/miR-34a/miR-16 axis. Furthermore, in vivo experiments conducted in a xenograft model in immunosuppressed Balb/c mice also proved the efficacy of the nanoparticles as an antitumor agent against NSCLC. Thus, our findings cumulatively suggest that the transferrin-adorned TQ-Np successfully coupled two distinct miRNA pathways to potentiate the apoptotic death cascade in the very lethal NSCLC cells and also restricts the migration of these cells without imparting any significant toxicity, which occurs in the widely used chemotherapeutic combinations. Thereby, our findings rekindle new hopes for the development of improved targeted therapeutic options with specified molecular objectives for combating the deadly NSCLC.