Cluster of differentiation 44 (CD44) is a cell surface glycoprotein overexpressed in varieties of solid tumors including pancreatic, breast, ovary, brain, and lung cancers. It is a multi-structural glycoprotein of the cell surface which is majorly involved in cell proliferation, cell-to-cell interaction, cellular migration, inflammation, and generation of immune responses. Numerous studies focus on the development of nanocarriers for active targeting of the CD44 receptor to improve efficacy of targeting chemotherapy and achieve precise chemotherapy by defining the release, uptake, and accumulation of therapeutic agents. The CD44 receptor has a selective binding affinity towards hyaluronic and chondroitin sulfate (CS). Taking this into consideration, this review focused on the role of CD44 in cancer and its therapy using several nanocarriers such as polymeric/non-polymeric nanoparticles, dendrimer, micelles, carbon nanotubes, nanogels, nanoemulsions etc., for targeted delivery of several chemotherapeutic molecules and nucleic acid. This review also illuminates the role of hyaluronic acid (HA) in cancer therapy, interaction of HA with CD44, and various approaches to target CD44-overexpressed neoplastic cells.

The goal of the current study is to develop a chitosan alginate nanoparticle system encapsulating the model drug, simvastatin (SIM-CA-NP) using a novel polyelectrolytic complexation method. The formulation was optimized using the central composite design by considering the concentrations of chitosan and alginate at five different levels (coded as +1.414, +1, 0, −1, and −1.414) in achieving minimum particle size (PS-Y1) and maximum entrapment efficiency (EE-Y2). A total of 13 runs were formulated (as projected by the Design-Expert software) and evaluated accordingly for the selected responses. On basis of the desirability approach (D = 0.880), a formulation containing 0.258 g of chitosan and 0.353 g of alginate could fulfill the prerequisites of optimum formulation in achieving 142.56 nm of PS and 75.18% EE. Optimized formulation (O-SIM-CAN) was further evaluated for PS and EE to compare with the theoretical results, and relative error was found to be within the acceptable limits, thus confirming the accuracy of the selected design. SIM release from O-SIM-CAN was retarded significantly even beyond 96 h, due to the encapsulation in chitosan alginate carriers. The cell viability study and Caspase-3 enzyme assay showed a notable difference in contrast to that of plain SIM and control group. All these stated results confirm that the alginate-chitosan nanoparticulate system enhanced the anti-proliferative activity of SIM.

Neurodegenerative disorders encompass a wide range of pathological conditions caused by progressive damage to the neuronal cells and nervous-system connections, which primarily target neuronal dysfunction and result in problems with mobility, cognition, coordination, sensation, and strength. Molecular insights have revealed that stress-related biochemical alterations such as abnormal protein aggregation, extensive generation of reactive oxygen and nitrogen species, mitochondrial dysfunction, and neuroinflammation may lead to damage to neuronal cells. Currently, no neurodegenerative disease is curable, and the available standard therapies can only provide symptomatic treatment and delay the progression of the disease. Interestingly, plant-derived bioactive compounds have drawn considerable attention due to their well-established medicinal properties, including anti-apoptotic, antioxidant, anti-inflammatory, anticancer, and antimicrobial properties, as well as neuroprotective, hepatoprotective, cardioprotective, and other health benefits. Plant-derived bioactive compounds have received far more attention in recent decades than synthetic bioactive compounds in the treatment of many diseases, including neurodegeneration. By selecting suitable plant-derived bioactive compounds and/or plant formulations, we can fine tune the standard therapies because the therapeutic efficacy of the drugs is greatly enhanced by combinations. A plethora of in vitro and in vivo studies have demonstrated plant-derived bioactive compounds’ immense potential, as proven by their capacity to influence the expression and activity of numerous proteins implicated in oxidative stress, neuroinflammation, apoptosis, and aggregation. Thus, this review mostly focuses on the antioxidant, anti-inflammatory, anti-aggregation, anti-cholinesterase, and anti-apoptotic properties of several plant formulations and plant-derived bioactive compounds and their molecular mechanisms against neurodegenerative disorders.

Wounds are the most common causes of mortality all over the world. Topical drug delivery systems are more efficient in treating wounds as compared to oral delivery systems because they bypass the disadvantages of the oral route. The aim of the present study was to formulate and evaluate in vitro in vivo nanoemulgels loaded with eucalyptol for wound healing. Nanoemulsions were prepared using the solvent emulsification diffusion method by mixing an aqueous phase and an oil phase, and a nanoemulgel was then fabricated by mixing nanoemulsions with a gelling agent (Carbopol 940) in a 1:1 ratio. The nanoemulgels were evaluated regarding stability, homogeneity, pH, viscosity, Fourier-transform infrared spectroscopy (FTIR), droplet size, zeta potential, polydispersity index (PDI), spreadability, drug content, in vitro drug release, and in vivo study. The optimized formulation, F5, exhibited pH values between 5 and 6, with no significant variations at different temperatures, and acceptable homogeneity and spreadability. F5 had a droplet size of 139 ± 5.8 nm, with a low polydispersity index. FTIR studies showed the compatibility of the drug with the excipients. The drug content of F5 was 94.81%. The percentage of wound contraction of the experimental, standard, and control groups were 100% ± 0.015, 98.170% ± 0.749, and 70.846% ± 0.830, respectively. Statistically, the experimental group showed a significant difference (p < 0.03) from the other two groups. The results suggest that the formulated optimized dosage showed optimum stability, and it can be considered an effective wound healing alternative.

Three-dimensional (3D) printing is a technique where the products are printed layer-by-layer via a series of cross-sectional slices with the exact deposition of different cell types and biomaterials based on computer-aided design software. Three-dimensional printing can be divided into several approaches, such as extrusion-based printing, laser-induced forward transfer-based printing systems, and so on. Bio-ink is a crucial tool necessary for the fabrication of the 3D construct of living tissue in order to mimic the native tissue/cells using 3D printing technology. The formation of 3D software helps in the development of novel drug delivery systems with drug screening potential, as well as 3D constructs of tumor models. Additionally, several complex structures of inner tissues like stroma and channels of different sizes are printed through 3D printing techniques. Three-dimensional printing technology could also be used to develop therapy training simulators for educational purposes so that learners can practice complex surgical procedures. The fabrication of implantable medical devices using 3D printing technology with less risk of infections is receiving increased attention recently. A Cancer-on-a-chip is a microfluidic device that recreates tumor physiology and allows for a continuous supply of nutrients or therapeutic compounds. In this review, based on the recent literature, we have discussed various printing methods for 3D printing and types of bio-inks, and provided information on how 3D printing plays a crucial role in cancer management.

Mucoadhesive polymers have an essential role in drug localization and target-specific actions in oral delivery systems. The current work aims to develop and characterize a new mucoadhesive polysaccharide polymer (thiolated xanthan gum-TXG and S-Protected thiolated xanthan gum-STX) that was further utilized for the preparation of repaglinide mucoadhesive tablets. The thiolation of xanthan gum was carried out by ester formation through the reaction of the hydroxyl group of xanthan gum and the carboxyl group of thioglycolic acid. Synthesis of TXG was optimized using central composite design, and TXG prepared using 5.303 moles/L of TGA and 6.075 g/L of xanthan gum can accomplish the prerequisites of the optimized formulation. Consequently, TXG was further combined with aromatic 2-mercapto-nicotinic acid to synthesize STX. TXG and STX were further studied for Fourier-transform infrared spectroscopy, rheological investigations, and Ellman’s assay (to quantify the number of thiol/disulfide groups). A substantial rise in the viscosity of STX might be due to increased interactions of macromolecules liable for improving the mucosal adhesion strength of thiolated gum. STX was proven safe with the support of cytotoxic study data. Mucoadhesive formulations of repaglinide-containing STX showed the highest ex vivo mucoadhesion strength (12.78 g-RSX-1 and 17.57 g- RSX-2) and residence time (>16 h). The improved cross-linkage and cohesive nature of the matrix in the thiolated and S-protected thiolated formulations was responsible for the controlled release of repaglinide over 16 h. The pharmacokinetic study revealed the greater AUC (area under the curve) and long half-life with the RSX-2 formulation, confirming that formulations based on S-protected thiomers can be favorable drug systems for enhancing the bioavailability of low-solubility drugs.

The use of essential oil–based nanoemulsions (NEs) has been the subject of extensive research on a variety of conditions affecting the oral cavity. NEs are delivery methods that improve the solubility and distribution of lipid medicines to the intended areas. Because of their antibacterial and antifungal properties, itraconazole and thyme oil–based self-nanoemulsifying drug delivery systems (ItZ-ThO-SNEDDS) were created to protect oral health against oral microorganisms. The ItZ-ThO-SNEDDS were created utilizing an extreme verices mixture design, and varying concentrations of ThO (10% and 25%), labrasol (40% and 70%), and transcutol (20% and 40%) were used. The ItZ-ThO-SNEDDS had droplet sizes of less than 250 nm, a drug-loading efficiency of up to 64%, and a fungal growth inhibition zone of up to 20 mm. The accepted design was used to obtain the ideal formulation, which contained ThO in the amount of 0.18 g/ml, labrasol 0.62 g/ml, and transcutol 0.2 g/ml. The best ItZ-ThO-SNEDDS formulation was incorporated into a honey-based gel, which demonstrated improved release of ItZ in vitro and improved transbuccal permeation ex vivo . In addition, when compared with various formulations tested in rats, the optimized loaded emulgel decreased the ulcer index. This study therefore demonstrated that the ItZ-ThO-SNEDDS could offer an effective defense against oral diseases caused by microbial infections.

Fungal eye infections are largely disseminated, especially in developing countries where they may leave over half a million people blind per year. The current study aims to boost the voriconazole antifungal efficiency via loading it as cubosomes (VZ-Cub) into hyaluronic acid and poloxamer-based ocular in situ gel. VZ-Cub were fabricated applying Box-Behnken design and employing phytantriol, poloxamer F127, and VZ amounts as independent variables. The produced nano vesicles were evaluated for the dependent variables of particle size (PS), entrapment efficiency (EE%), and transcorneal steady-state flux (Jss) of the VZ, and, the obtained optimal VZ-Cub was loaded into an in situ gel base to enhance its ocular residence time. The in situ gel formulation was tested for its gelation temperature, drug release behavior, transcorneal permeation effects, and antifungal activity. The optimized VZ-Cub consisted of 100 mg of phytantriol, 60 mg of poloxamer F127, and 21 mg of VZ. This formulation led to a minimum PS of 71 nm, an EE% of 66%, Jss value of 6.5 µg/(cm2·min), and stability index of 94 ± 2%. The optimized VZ-Cub-loaded in situ gel released 84% VZ after 12 h and yielded a 4.5-fold increase in drug permeation compared with the VZ aqueous dispersion. The antifungal activity, which was obtained by measuring the fungal growth inhibition zones, revealed that the VZ-Cub-loaded in situ gel formulation had a 3.89-fold increase in antifungal activity compared with the VZ dispersion. In summary, an ocular in situ gel loaded with VZ-Cub could be an effective novel nano-paradigm with enhanced transcorneal permeation and antifungal properties.