Folate-Mediated Targeting and Controlled Release: PLGA-Encapsulated Mesoporous Silica Nanoparticles Delivering Capecitabine to Pancreatic Tumor.

The discovery of specifically tailored therapeutic delivery systems has sparked the interest of pharmaceutical researchers considering improved therapeutic effectiveness and fewer adverse effects. The current study concentrates on the design and characterization of PLGA (polylactic-co-glycolic acid) capped mesoporous silica nanoparticles (MSN)-based systems for drug delivery for pH-sensitive controlled drug release in order to achieve a targeted drug release inside the acidic tumor microenvironment. The physicochemical properties of the nanoformulations were analyzed using TEM, zeta potential, AFM, TGA, FTIR, and BET analyses in addition to DLS size. The final formed PLGA-FoA-MSN-CAP and pure MSN had sizes within the therapeutic ranges of 164.5 ± 1.8 and 110.7 ± 2.2, respectively. Morphological characterization (TEM and AFM) and elemental analysis (FTIR and XPS) confirmed the proper capping and tagging of PLGA and folic acid (FoA). The PLGA-coated FoA-MSN exhibited a pH-dependent controlled release of the CAP (capecitabine) drug, showing efficient release at pH 6.8. Furthermore, the in vitro MTT test on PANC1 and MIAPaCa-2 resulted in an IC50 value of 146.37 µg/ml and 105.90 µg/ml, respectively. Mitochondrial-mediated apoptosis was confirmed from the caspase-3 and annexin V/PI flow cytometry assay, which displayed a cell cycle arrest at the G1 phase. Overall, the results predicted that the designed nanoformulation is a potential therapeutic agent in treating pancreatic cancer.

Graphene-silymarin-loaded chitosan/gelatin/hyaluronic acid hybrid constructs for advanced full-thickness burn wound management.

Burn wounds (BWs) with extensive blood loss, along with bacterial infections and poor healing, may become detrimental and pose significant rehabilitation obstacles in medical facilities. Therefore, the freeze-drying method synthesized novel hemocompatible chitosan, gelatin, and hyaluronic acid infused with graphene oxide-silymarin (CGH-SGO) hybrid constructs for application as a BW patch. Most significantly, synthesized hybrid constructs exhibited an interconnected-porous framework with precise pore sizes (≈118.52 µm) conducive to biological functions. Furthermore, the FTIR and XRD analyses document the constructs' physiochemical interactions. Similarly, enhanced swelling ratios, adequate WVTR (736 ± 78 g m-2 hr-1), and bio-degradation rates were seen during the physiological examination of constructs. Following the in vitro investigations, SMN-GO added to constructs improved their anti-bacterial (against E.coli and S. aureus), anti-oxidant, hemocompatible, and bio-compatible characteristics in conjunction with prolonged drug release. Furthermore, in vivo, implanting constructs on wounds exhibited significant acceleration in full-thickness burn wound (FT-BW) healing on the 14th day (CGH-SGO: 95 ± 2.1 %) in contrast with the control (Gauze: 71 ± 4.2 %). Additionally, contrary to gauze, the in vivo rat tail excision model administered with constructs assured immediate blood clotting. Therefore, CGH-SGO constructs with an improved porous framework, anti-bacterial activity, hemocompatibility, and biocompatibility could represent an attractive option for healing FT-BWs.

In vitro and in vivo assessment of curcumin-quercetin loaded multi-layered 3D-nanofibroporous matrix prepared by solution blow-spinning for full-thickness burn wound healing.

Burn wounds (BWs) cause impairment of native skin tissue and may cause significant microbial infections that demand immediate care. Curcumin (Cur) and quercetin (Que) exhibit antimicrobial, hemocompatibility, ROS-scavenging, and anti-inflammatory properties. However, its instability, water insolubility, and low biological fluid absorption render it challenging to sustain local Cur and Que doses at the wound site. Therefore, to combat these limitations, we employed blow-spinning and freeze-drying to develop a multi-layered, Cur/Que-loaded gelatin/chitosan/PCL (GCP-Q/C) nanofibroporous (NFP) matrix. Morphological analysis of the NFP-matrix using SEM revealed a well-formed multi-layered structure. The FTIR and XRD plots demonstrated dual-bioactive incorporation and scaffold polymer interaction. Additionally, the GCP-Q/C matrix displayed high porosity (82.7 ± 2.07 %), adequate pore size (∼121 µm), enhanced water-uptake ability (∼675 % within 24 h), and satisfactory biodegradation. The scaffolds with bioactives had a long-term release, increased antioxidant activity, and were more effective against gram-positive (S. aureus) and gram-negative (E. coli) bacteria than the unloaded scaffolds. The in vitro findings of GCP-Q/C scaffolds showed promoted L929 cell growth and hemocompatibility. Additionally, an in vivo full-thickness BW investigation found that an implanted GCP-Q/C matrix stimulates rapid recuperation and tissue regeneration. In accordance with the findings, the Gel/Ch/PCL-Que/Cur NFP-matrix could represent an effective wound-healing dressing for BWs.

Glypican1: A potential cancer biomarker for nanotargeted therapy.

Glypicans (GPCs) are generally involved in cellular signaling, growth and proliferation. Previous studies reported their roles in cancer proliferation. GPC1 is a co-receptor for a variety of growth-related ligands, thereby stimulating the tumor microenvironment by promoting angiogenesis and epithelial-mesenchymal transition (EMT). This work reviews GPC1-biomarker-assisted drug discovery by the application of nanostructured materials, creating nanotheragnostics for targeted delivery and application in liquid biopsies. The review includes details of GPC1 as a potential biomarker in cancer progression as well as a potential candidate for nano-mediated drug discovery.

Novel strategies for designing regenerative skin products for accelerated wound healing.

Healthy skin protects from pathogens, water loss, ultraviolet rays, and also maintains homeostasis conditions along with sensory perceptions in normal circumstances. Skin wound healing mechanism is a multi-phased biodynamic process that ultimately triggers intercellular and intracellular mechanisms. Failure to implement the normal and effective healing process may result in chronic injuries and aberrant scarring. Chronic wounds lead to substantial rising healthcare expenditure, and innovative methods to diagnose and control severe consequences are urgently needed. Skin tissue engineering (STE) has achieved several therapeutic accomplishments during the last few decades, demonstrating tremendous development. The engineered skin substitutes provide instant coverage for extensive wounds and facilitate the prevention of microbial infections and fluid loss; furthermore, they help in fighting inflammation and allow rapid neo-tissue formation. The current review primarily focused on the wound recovery and restoration process and the current conditions of STE with various advancements and complexities associated with different strategies such as cell sources, biopolymers, innovative fabrication techniques, and growth factors delivery systems.

Design strategies for composite matrix and multifunctional polymeric scaffolds with enhanced bioactivity for bone tissue engineering.

Over the past few decades, various bioactive material-based scaffolds were investigated and researchers across the globe are actively involved in establishing a potential state-of-the-art for bone tissue engineering applications, wherein several disciplines like clinical medicine, materials science, and biotechnology are involved. The present review article's main aim is to focus on repairing and restoring bone tissue defects by enhancing the bioactivity of fabricated bone tissue scaffolds and providing a suitable microenvironment for the bone cells to fasten the healing process. It deals with the various surface modification strategies and smart composite materials development that are involved in the treatment of bone tissue defects. Orthopaedic researchers and clinicians constantly focus on developing strategies that can naturally imitate not only the bone tissue architecture but also its functional properties to modulate cellular behaviour to facilitate bridging, callus formation and osteogenesis at critical bone defects. This review summarizes the currently available polymeric composite matrices and the methods to improve their bioactivity for bone tissue regeneration effectively.