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Existing therapies yield low drug encapsulation or accumulation in the lungs, hence the site-specific drug delivery remains the challenge for tuberculosis. Lately, dry powder inhalers (DPIs) are showing promising drug deposition in the deeper lung tissues. Biocompatible polymers with the ability to naturally recognize and bind to the surface receptors of alveolar macrophages, the reservoir of the causative organism, were selected. DPIs comprised of chitosan (CS)/thiolated chitosan (TC) in conjugation with Hyaluronic acid (HA) were synthesized loaded with isoniazid (INH) by using the Design of Experiment (DoE) approach. Nanosuspensions were prepared by ionic gelation method using cross-linker, sodium-tripolyphosphate (TPP) and were optimized by using Box-Behnken 3-level screening design and later freeze-dried to obtain nanopowders. Physico-chemical compatibility of nanoplex systems was investigated using in-vitro characterization techniques. In-vitro release and permeation studies were correlated in terms of the pattern of drug content dissolved over time. In addition, the cytotoxicity studies on A549 cells demonstrated the safety profile of the nanoplexes. Moreover, in-silico studies and aerodynamic profiles verify the suitability of DPIs for further in-vivo tuberculosis therapeutics. DoE analyses affirmed the lack of linearity in the model for the certain response of studied parameters in a holistic way, which was not possible else ways.

Mannose receptors (MR) are highly over-expressed on macrophages in the inflammatory bowel disease (IBD) and can be targeted by developing mannose-anchored nano-carrier system. In this study, mannosylated chitosan (MC) polymer was synthesized because of its high affinity for mannose receptors. Afterward, MC nanoparticles (NPs) were fabricated encapsulating dexamethasone to target macrophages for attenuation of inflammation at initial stages. Further, NPs were coated with a pH-sensitive polymer to control the premature drug release in the stomach. NPs were optimized using a surface response quadratic model to study the impact of various process parameters. Optimized NPs were then characterized for size, morphology, zeta potential, surface chemistry, biocompatibility, and uptake by macrophages. The average particle size was found to be 380 ± 19.8 nm with an encapsulation efficiency of 78.1 ± 1.17%. pH-dependent drug release profile was obtained with an average release of 73.9 ± 5.24% over 72 h in simulated intestinal fluid (pH 7.4). Moreover, the NPs uptake by the macrophages supported the viability of macrophages with the NPs and did not show any adverse effects. Moreover, this study was supported by the uptake of NPs inside macrophages. Altogether, the data supported that MC NPs could serve as a potential anti-inflammatory therapeutic approach to target macrophages in IBD.

The two types ofncRNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are responsible for several biological processes within cells, such as the immune responses, cell growth and invasion, and regulation of the cell cycle. Rapidly expanding class of ncRNAs, lncRNAsinteract with other molecules to form chromatin-remodeling complexes. These potential hallmarks of diseases contribute to transcriptional and post-transcriptional regulation of several genes, possibly via cross-talk with other RNAs. Aberrant expression of lncRNAshas drawn increasing attention to the pathophysiology of different diseases, includingcancer and cardiovasculardiseases. Unfortunately, circulating lncRNAs are presented in the bloodstream at very low levels, making sensitive detection difficult. Currently, there are few methods for detecting these ncRNAs from which quantitative real-time-polymerase chain reaction (qRT-PCR) is the most routinely used technique. These techniqueslack sensitivity for intracellular detection of lncRNAs. Moreover, they are tedious and require a large sample size. Currently, nanotechnology has taken over the diagnostic field because of the tunable properties and modification opportunities. Furthermore, these conventional techniques can be merged with nanotechnology to improve detection sensitivity.This review highlights some of the most recent findings on nanotechnology-based methods and possible obstacles intheir application for moreaccurate sensing of lncRNAs.

Osteosarcoma (OSA) is a type of bone cancer that begins in the cells that form bones. OSA is a rare mesenchymal bone neoplasm derived from mesenchymal stem cells. Genome disorganization, chromosomal modifications, deregulation of tumor suppressor genes, and DNA repair defects are the factors most responsible for OSA development. Despite significant advances in the diagnosing and treatment of OSA, patients’ overall survival has not improved within the last twenty years. Lately, advances in modern nanotechnology have spurred development in OSA management and offered several advantages to overcome the drawbacks of conventional therapies. This technology has allowed the practical design of nanoscale devices combined with numerous functional molecules, including tumor-specific ligands, antibodies, anti-cancer drugs, and imaging probes. Thanks to their small sizes, desirable drug encapsulation efficiency, and good bioavailability, functionalized nanomaterials have found wide-spread applications for combating OSA progression. This review invokes the possible utility of engineered nanomaterials in OSA diagnosis and treatment, motivating the researchers to seek new strategies for tackling the challenges associated with it.

The development of effective strategies for local administration of chemotherapeutic drugs, thus minimizing the adverse side effects to patients, is one of the key challenges in biomedicine and cancer research. This work reports the formulation and characterization of PluronicF127 microemulsions to enhance the bioavailability of Cisplatin (Cis). The size of Cis microemulsion was about 12.0 nm, as assessed by dynamic light scattering analysis. In vitro cytotoxic activity of free Cis and F127/Cis microemulsions were studied on malignant (C152 and MCF7) and normal (HUVEC) cells via tetrazolium (MTT) colorimetric assay. Cell morphology was also monitored. In vitro assessments revealed thatF127/Cis microemulsions induced cytotoxicity/morphological changes to a lesser extent than free Cis. Regarding in vivo experiments, F127/Cis microemulsions were injected intraperitoneally at 7 and 14 mg/kg doses into adult male Wistar rats to assess histologic and biochemical changes. In this case, the bulk Cis group caused severe histopathological changes and significant increases in serum liver enzymes and serum kidney function markers. The group treated with the 14 mg/kg dose of F127/Cis microemulsions also showed severe fatty changes and significant increases in serum liver enzymes, blood urea nitrogen, and creatinine levels. The group treated with the low dose of nano-Cis showed a significant increase in serum liver enzymes levels accompanied by mild fatty changes of the liver. Theoretical surveys were performed to get an understanding of the interplay between F127 and Cis. Results reveal that hydrogen bonding (HB) interactions with F127have an influence on the molecular properties of Cis and may playa role in the lower toxicity of F127/Cis in comparison to free Cis.

The blood–brain barrier (BBB) is the protective sheath around the brain that protects the sensitive microenvironments of the brain. However, certain pathogens, viruses, and bacteria disrupt the endothelial barrier and cause infection and hence inflammation in meninges. Macromolecular therapeutics are unable to cross the tight junctions, thereby limiting their bioavailability in the brain. Recently, nanotechnology has brought a revolution in the field of drug delivery in brain infections. The nanostructures have high targeting accuracy and specificity to the receptors in the case of active targeting, which have made them the ideal cargoes to permeate across the BBB. In addition, nanomaterials with biomimetic functions have been introduced to efficiently cross the BBB to be engulfed by the pathogens. This review focuses on the nanotechnology-based drug delivery approaches for exploration in brain infections, including meningitis. Viruses, bacteria, fungi, or, rarely, protozoa or parasites may be the cause of brain infections. Moreover, inflammation of the meninges, called meningitis, is presently diagnosed using laboratory and imaging tests. Despite attempts to improve diagnostic instruments for brain infections and meningitis, due to its complicated and multidimensional nature and lack of successful diagnosis, meningitis appears almost untreatable. Potential for overcoming the difficulties and limitations related to conventional diagnostics has been shown by nanoparticles (NPs). Nanomedicine now offers new methods and perspectives to improve our knowledge of meningitis and can potentially give meningitis patients new hope. Here, we review traditional diagnosis tools and key nanoparticles (Au-NPs, graphene, carbon nanotubes (CNTs), QDs, etc.) for early diagnosis of brain infections and meningitis.

Nanomaterials are attracting increasing interest in many biomedical fields, including the fight against cancer. In this context, we successfully synthesized CoNi alloy nanoparticles (NPs) by a simple polyol process. The magnetic characteristics of the products were measured by vibration sample magnometry, which revealed that the samples have soft ferromagnetic behavior. The microstructure and morphology were inspected by X-ray diffraction and scanning electron microscopy, respectively. Human cancer cells derived from the breast (MCF7) and oral cavity (C152) and normal cells derived from human umbilical vein endothelial cells (HUVECs) were treated with increasing concentrations of CoNi NPs, and their cytotoxic effect was measured via MTT and lactate dehydrogenase (LDH) leakage assays. We found that treatments by using 12.5 to 400 µg/mL of Co0.5Ni0.5, Co0.6Ni0.4, and Co0.4Ni0.6 NPs were associated with significant concentration-dependent toxicity toward such cell lines and profoundly enhanced LDH leakage following 48 h of exposure (P

Brain tumors, especially glioblastoma, remain the most aggressive form of all the cancers because of inefficient diagnosis and profiling. Nanostructures, such as metallic nanostructures, silica nano-vehicles, quantum dots, lipid nanoparticles (NPs) and polymeric NPs, with high specificity have made it possible to permeate the blood–brain barrier (BBB). NPs possess optical, magnetic and photodynamic properties that can be exploited by surface modification, bio composition, contrast agents’ encapsulation and coating by tumor-derived cells. Hence, nanotechnology has brought on a revolution in the field of diagnosis and imaging of brain tumors and cancers. Recently, nanomaterials with biomimetic functions have been introduced to efficiently cross the BBB to be engulfed by deep skin tumors and cancer malignancies for imaging. The review focuses on nanotechnology-based diagnostic and imaging approaches for exploration in brain tumors and cancers. Moreover, the review also summarizes a few strategies to image glioblastoma and cancers by multimodal functional nanocomposites for more precise and accurate clinical diagnosis. Their unique physicochemical attributes, including nanoscale sizes, larger surface area, explicit structural features and ability to encapsulate diverse molecules on their surface, render nanostructured materials as excellent nano-vehicles to cross the blood–brain barrier and convey drug molecules to their target region. This review sheds light on the current progress of various kinds of nanomaterials, such as liposomes, nano-micelles, dendrimers, carbon nanotubes, carbon dots and NPs (gold, silver and zinc oxide NPs), for efficient drug delivery in the treatment and diagnosis of brain cancer.

Chitosan (CS) is a natural biopolymer used frequently in drug delivery because of its biodegradability and biocompatibility. Several derivatives of CS have also been synthesized to improve the mucoadhesion and solubility of the nascent CS. The nano and micro particles are reported to have enhanced drug bioavailability, solubility and permeation. Recently, there is an advancement in the active targeted drug and gene delivery using CS because of its tunable surface modifications. This review focuses on CS and its chemically modified structures along with their different nanostructures with examples from the most exploited routes of administration. Herein, the functionalization of CS nanoparticles has also been enlisted along with the use of CS in the immunotherapy as vaccine carriers. Beside, few patents, ongoing clinical trials and already marketed CS-based products are also enlisted.

Nanotechnology has revolutionized novel drug delivery strategies through establishing nanoscale drug carriers, such as niosomes, liposomes, nanomicelles, dendrimers, polymeric micelles, and nanoparticles (NPs). Owing to their desirable cancer-targeting efficacy and controlled release, these nanotherapeutic modalities are broadly used in clinics to improve the efficacy of small-molecule inhibitors. Poly(ADP-ribose) polymerase (PARP) family members engage in various intracellular processes, including DNA repair, gene transcription, signal transduction, cell cycle regulation, cell division, and antioxidant response. PARP inhibitors are synthetic small-molecules that have emerged as one of the most successful innovative strategies for targeted therapy in cancer cells harboring mutations in DNA repair genes. Despite these advances, drug resistance and unwanted side effects are two significant drawbacks to using PARP inhibitors in the clinic. Recently, the development of practical nanotechnology-based drug delivery systems has tremendously improved the efficacy of PARP inhibitors. NPs can specifically accumulate in the leaky vasculature of the tumor and cancer cells and release the chemotherapeutic moiety in the tumor microenvironment. On the contrary, NPs are usually unable to permeate across the body's normal organs and tissues; hence the toxicity is zero to none. NPs can modify the release of encapsulated drugs based on the composition of the coating substance. Delivering PARP inhibitors without modulation often leads to the toxic effect; therefore, a delivery vehicle is essential to encapsulate them. Various nanocarriers have been exploited to deliver PARP inhibitors in different cancers. Through this review, we hope to cast light on the most innovative advances in applying PARP inhibitors for therapeutic purposes., Comunidad de Madrid

Aim: To fabricate and evaluate the therapeutic efficacy of glycyrrhizic acid (GA)-loaded pH-sensitive nanoformulations that specifically target and combat mucosal inflammation of the colon. Methods: GA-loaded Eudragit® S100/poly-(lactic-co-glycolic acid) nanoparticles were developed through modified double-emulsion evaporation coupled with solvent evaporation coating techniques and analyzed for physicochemical characteristics, surface chemistry, release kinetics, site-retention and therapeutic effectiveness. Results: Nanoparticles have a particle size of approximately 200 nm, high encapsulation efficiency, desired surface chemistry with pH-dependent and sustained drug release behavior following the Gompertz kinetic model. In vivo retention and therapeutic effectiveness in the inflamed colon tissues were confirmed by macroscopic and microscopic indices, cytokine analysis and antioxidant assays. Conclusion: GA-loaded Eudragit S100/poly-(lactic-co-glycolic acid) nanoparticles could efficiently deliver GA to the colon and ameliorate the mucosal inflammation for a prolonged duration.

Recruited macrophages in inflammation attract various ligand-receptor drug delivery approaches. Galactose bound nanocarriers are promising to catch macrophages because of surface-expressed macrophage galactose type-lectin-C (MGL-2) receptor. The present study reported fabrication of galactose conjugated PLGA (GAL-PLGA) polymer and nanoparticles under quality by design (QBD) approach to investigate macrophages targeting potential at inflamed intestine. GAL-PLGA nanoparticles were fabricated through O/W emulsion-evaporation method under QBD approach and Box-Behnken design. Obtained GAL-PLGA nanoparticles have optimum particle size (~118 nm), drug entrapment (87%) and zeta potential (−9.5). TGA, XPRD and FTIR confirmed stability and negate drug-polymer interactions. Further, nanoparticles have considerable hemocompatibility, biocompatibility and cellular uptake; macrophage uptake was inhibited by D-galactose confirming involvement of MGL-2. Moreover, drug retention studies in the DSS-colitis model provide background for potential of nanoparticles to target and reside inflamed intestine. It is concluded that GAL-PLGA nanoparticles are suitable platform to target macrophages at the inflamed intestine through oral route.