Nanodroplets Engineered with Folate Carbon Dots for Enhanced Cancer Cell Uptake toward Theranostic Application.

The research in nanotherapeutics is rapidly advancing, particularly in the realm of nanoconstructs for drug delivery. This study introduces folate-based carbon dot-decorated nanodroplets (f-Dnm), synthesized from a binary mixture of negatively charged folic acid carbon dots (f-CDs) and cationic-branched polyethylenimine (PEI). The uniformly spherical nanodroplets with an average diameter of 115 ± 15 nm exhibit notable photoluminescence. Surface potential analysis reveals a significant change upon coacervation, attributed to strong electrostatic interactions between f-CD and PEI. The engineered nanodroplets show excellent colloidal and photostability even after 6 months of storage at room temperature. The pH-dependent self-assembly and disassembly properties of f-Dnm are explored for drug loading and release studies using doxorubicin (DOX) as a model anticancer drug. Moreover, the f-Dnm nanocarrier demonstrates significantly higher drug loading capabilities (∼90%). In vitro release studies of doxorubicin-loaded f-Dnm [f-Dnm(DOX)] reveal 5 times higher drug release at lysosomal pH 5.4 compared to that at physiological blood pH 7.4. Cytocompatibility assessments using the MTT assay on HeLa, A549, and NIH-3T3 cells confirm the nontoxic nature of f-Dnm, even at high concentrations. Additionally, f-Dnm(DOX) exhibits higher cytotoxicity in HeLa cells compared to f-CD(DOX) at similar DOX concentrations. Cellular uptake studies show an increased uptake of f-Dnm in folate receptor-positive HeLa and MDA-MB 231 cells. Hemolysis assay validated the biocompatibility of the developed formulation. Overall, these engineered nanodroplets represent a class of nontoxic nanocarriers that offer promising potential as nanotherapeutics for folate receptor-positive cells.

Iron Nano Biocomposite-Infused Biopolymeric Films: A Multifunctional Approach for Robust Skin Repair.

Sodium alginate (SA) biopolymeric films have various limitations such as poor mechanical properties, high vapor permeability, lack of antibacterial activity, excessive burst release, and weak cell adhesion. To overcome these limitations, a strategy involving the integration of nanofillers into an SA film matrix is explored. In this context, a cost-effective iron-containing carbon nano biocomposite (FeCNB) nanofiller is developed using a solvent-free technique. This nanocomposite is successfully incorporated into the alginate film matrix at varying concentrations (0.05, 0.1, and 0.15%) aimed at enhancing its physicochemical and biological properties for biomedical applications. Characterization through FESEM and BET analyses confirms the porous nature of the FeCNB. EDX shows the FeCNB's uniform distribution upon its integration into the film matrix, albeit without strong chemical interaction with SA. Instead, hydrogen bonding interactions become apparent in the FTIR spectra. By incorporating the FeCNB, the mechanical attributes of the films are improved and the water vapor permeability approaches the desired range (2000-2500 g/m2day). The film's swelling ratio reduction contributes to a decrease in water permeability. The antibacterial activity and sustained release property of the FeCNB-incorporated film are established using tetracycline hydrochloride (TCl), a model drug. The drug release profile resembled Korsmeyer-Peppas's release pattern. In vitro assessments via the MTT assay and scratch assay on NIH-3T3 cells reveal that FeCNB has no adverse effects on the biocompatibility of alginate films. The cell proliferation and adhesion to the SA film are significantly enhanced after infusion of the FeCNB. The in vivo study performed on the rat model demonstrates improved wound healing by FeCNB-impregnated films. Based on the comprehensive findings, the proposed FeCNB-incorporated alginate films prove to be a promising candidate for robust skin repair.

TiB2-Derived Nanosheets Enhance the Tensile Strength and Controlled Drug Release of Biopolymeric Films Used in Wound Healing.

Wound healing using an alginate-based biopolymeric film is one of the most preferred treatments. However, these films lack mechanical strength (elasticity and tensile strength), show higher initial burst release, and exhibit high vapor permeability. The present study reports the development of nanosheets derived from titanium diboride (10 nm) (NTB)-incorporated biopolymeric films (0.025, 0.05, and 0.1% w/v) using sodium alginate (SA) and carboxymethyl cellulose (CMC) to overcome the shortfalls. The surface properties of the film, nanosheet distribution within the film, and possible interactions with the film are explored by using scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), Fourier transform infrared (FTIR), and X-ray diffraction (XRD). These analyses confirm that nanosheets are uniformly distributed in the film and introduce unevenness on the film's surface. The tensile strength of the nanosheet-incorporated film (0.1% NTB film) using UTM is found to be 24.30 MPa (six times higher compared to the blank film), equivalent to human skin. The water vapor transmission rate of the film is also found to be in the desired range (i.e., 2000-2500 g/m2 day). The biocompatibility of the NTB film is confirmed by the MTT assay test using NIH/3T3 cells and HEK 293 cells. Furthermore, the scratch assay shows that the developed films promote cell migration and proliferation. The antibacterial activity of the film is also demonstrated using a model drug, tetracycline hydrochloride (TCl). Besides, the film exhibits the sustained release of TCl and follows the Korsmeyer-Peppas model for drug release. Overall, the 0.1% w/v NTB film is easy to fabricate, biocompatible and shows superior mechanical properties.

Self-Assembled Amino Acid Microstructures as Biocompatible Physically Unclonable Functions (BPUFs) for Authentication of Therapeutically Relevant Hydrogels.

Counterfeited biomedical products result in significant economic losses and pose a public health hazard for over a million people yearly. Hydrogels, a class of biomedical products, are being investigated as alternatives to conventional biomedical products and are equally susceptible to counterfeiting. Here, a biocompatible, physically unclonable function (BPUF) to verify the authenticity of therapeutically relevant hydrogels are developed. The principle of BPUF relies on the self-assembly of tyrosine into fibril-like structures which are incorporated into therapeutically relevant hydrogels resulting in their random dispersion. This unclonable arrangement leads to distinctive optical micrographs captured using an optical microscope. These optical micrographs are transformed into a unique security code through cryptographic techniques which are then used to authenticate the hydrogel. The temporal stability of the BPUFs are demonstrated and additionally, exploit the dissolution propensity of the structures upon exposure to an adulterant to identify the tampering of the hydrogel. Finally, a platform to demonstrate the translational potential of this technology in validating and detecting tampering of therapeutically relevant hydrogels is developed. The potential of BPUFs to combat hydrogel counterfeiting is exemplified by its simplicity in production, ease of use, biocompatibility, and cost-effectiveness.

Application of Twin-Screw Melt Granulation to Overcome the Poor Tabletability of a High Dose Drug.

Pharmaceutical tablet manufacturing has seen a paradigm shift toward continuous manufacturing and twin-screw granulation-based technologies have catalyzed this shift. Twin-screw granulator can simultaneously perform unit operations like mixing, granulation, and drying of the granules. The present study investigates the impact of polymer concentration and processing parameters of twin-screw melt granulation, on flow properties and compaction characteristics of a model drug having high dose and poor tabletability. Acetaminophen (AAP) and polyvinylpyrrolidone vinyl acetate (PVPVA) were used as a model drug (90-95% w/w) and polymeric binder (5-10%w/w), respectively, for the current study. Feed rate (~650-1150 g/h), extruder screw speed (150-300 rpm), and temperature (60-150°C) were used as processing variables. Results showed the reduction in particle size of drug in the extrudates (D90 of 15-25 µm from ~80 µm), irrespective of processing condition, while flow properties were a function of polymer concentration. Overall, good flowability of the products and their tablets with optimum tensile strength can be obtained through using high polymer concentration (i.e., 10% w/w), lower feed rate (~650 g/h), lower extruder screw speed (150 rpm), and higher processing temperatures (up to 120°C). The findings from the current study can be useful for continuous manufacturing of tablets of high dose drugs with minimal excipient loading in the final dosage form.

Understanding molecular upsets in diabetic nephropathy to identify novel targets and treatment opportunities.

Diabetes and related complications are becoming a global encumbrance. Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD). The available therapeutic modalities related to DN do not treat DN at the molecular level, proposing further amendments in the management of DN based on the pathogenesis of DN. This manuscript discusses the concept and applications of nanomedicine for the treatment of DN that can improve renal targeting, retention and localization. This review also highlights the current issues related to targeting DN, challenges and allied opportunities toward the development of next-generation drugs and treatments for the management of DN.

Budding Alliance of Nanotechnology in RNA Interference Therapeutics.

RNA interference (RNAi), as a novel technique in which RNA molecules limit or silence the gene expression, is currently a hot research topic for producing novel therapeutic materials for challenging diseases. In the development of RNAi-based therapies, nanoscale particles, with a varying diameter along with facile modification methods that can mediate effective RNAi with targeting potential, are gaining wide interest. The nanotechnology itself has tremendous potential in the field of healthcare, especially for the development of better pharmaceuticals. Nano-enabled delivery has shown great success in the delivery of RNAi based therapeutics to specific locations in the body. Especially, siRNAs show great potential for use in nucleic acid therapeutics because of their potent and specific RNAi-triggering activity. This review summarizes the advanced nanocarriers such as solid lipid nanoparticles, gold nanoparticles, silver nanoparticles, iron oxide nanoparticles, polymeric nanoparticles, nanotransformers and curdlan nanoparticles with special emphasis on various aspects of siRNA-based therapeutics.