Current Nanomedicine - Volume 11, Issue 4, 2021

Poor solubility of a drug is one of the major concerns in drug delivery. Many strategies have been employed for solving this problem, but there are still some deficiencies with current strategies, such as low drug loading, high toxicity, poor stability, potential drug loss during storage, and complex manufacturing method. By formulating nanocrystals, problems associated with the delivery of drugs with low water or lipid solubility can be addressed. Unlike polymeric nanoparticles and lipidic nanoparticles, they are not reservoir or matrix systems. Nanocrystals are colloidal suspensions of nanosized particles stabilized by polymeric or electrostatic stabilization. They can be prepared by Top-down or Bottom-up approaches. Some of the methods for the preparation of nanocrystals are nanoprecipitation, media milling, high-pressure homogenization, emulsions and microemulsions as templates, supercritical fluid technology, and co-grinding. They can be used for oral, intravenous, ocular, inhalation, intramuscular drug delivery and drug targeting.

Poor solubility of some medicinal compounds is a serious challenge that can be addressed by using a nano-suspension for improved delivery. The nanoparticles enhance the bioavailability along with the aqueous solubility of the drug, which is accomplished by increasing the active surface area of the drug. The gained attention of the nanosuspension is due to its stabilization facility, which is achieved by polymers, such as polyethylene glycol (PEG), having a particular size range of 10 - 100 nm. Hence, these nanoparticles have the capacity of binding to the targeted with very low damage to the healthy tissues. These are prepared by various methods, such as milling, high-pressure homogenization, and emulsification, along with melt emulsification. Moreover, surface modification and solidification have been used to add specific properties to the advanced therapies as post-processing techniques. For many decades, it has been known that water solubility hampers the bioavailability and not all drugs are water-soluble. In order to combat this obstacle, nanotechnology has been found to be of specific interest. For elevating the bioavailability by increasing the dissolution rate, the methodology of reduction of the associated drug particles into their subsequent submicron range is incorporated. For oral and non-oral administration, these nanosuspension formulations are used for the delivery of drugs.

Introduction: Rifampicin conjugated (R-CP) and rifampicin-isoniazid dual conjugated (RI-CP) norbornene-derived nanocarriers are newly designed for pH stimuli-responsive delivery of tuberculosis (TB) drugs. Its biosafety level is yet to be well established. Objectives: This study aimed to assess the impacts of the nanocarriers on liver cells using the zebrafish animal model and human liver cell line model (HepG2). Methods: Initially, lethal dose concentration for the norbornene-derived nanocarrier systems in zebrafish was determined. The toxic effects were analysed at the sub-lethal drug concentration by histopathological study, total GSH level, gene expression, and DNA damage in zebrafish liver cells. Fish erythrocyte nuclear abnormalities were also evaluated. Cell viability and oxidative stress level (ROS generation) after exposure to the nanoconjugates were determined using HepG2 cells in the in vitro study. Results: In vivo studies of both R-CP and RI-CP showed 100% mortality at 96 hours for exposure concentration >100mg/l and showed toxic changes in zebrafish liver histology, GSH, and DNA damage levels. Noticeably upregulated PXR, CYP3A, and cyp2p6 genes were observed in RI-CP exposure than in RIF or R-CP molecules. The in vitro study revealed a dose-dependent effect on cell viability and ROS generation for RIF, R-CP, and RI-CP exposures in HepG2 cells. Conclusion: The current study reports that the rifampicin conjugated (R-CP) and rifampicin-isoniazid conjugated (RI-CP) norbornene derived nanocarriers exhibit enhanced toxic responses in both adult zebrafish and HepG2 cells. The pH-sensitive norbornene-derived nanocarriers on conjugation with different drugs exhibited varied impacts on hepatic cells. Hence the present investigation recommends a complete metabolomics analysis and norbornene carrier-drug interaction study to be performed for each drug conjugated norbornene nanocarrier to ensure its biosafety.

Background: Diabetes mellitus is the most common health problem in the world. Silver nanoparticles (AgNPs) exposed great intrinsic anti-inflammatory, antibacterial, antiviral, and antifungal activities. Chitosan is an oligosaccharide biopolymer with a great ability to lower hyperglycemia, and ascorbic acid is a water-soluble vitamin with strong antioxidant activity. Objective: The present study aimed to estimate AgNPs/chitosan/ascorbic acid nanocomposite (Ag- NCs) anti-diabetic properties in streptozotocin-induced diabetic rats. Methods: Eighteen male Wistar albino rats were divided into three main groups (6 rats/group); control, diabetic, and Ag-NCs groups. Control group: after a single dose of citrate buffer at PH 4.5 (0.1 mol/L, i.p), the rats orally received 1 ml distilled water daily for four weeks. The diabetic model was induced by a single dose of streptozotocin (60 mg/kg, i.p) for type 1 diabetes and the rats orally received 1 ml distilled water daily for four weeks. The diabetic group was treated orally with Ag-NCs (0.25 mg/Kg body weight) daily for four weeks. Results: AgNPs/chitosan/ascorbic acid nanocomposite group showed a reduction in the concentrations of glucose, NO, MDA, LDL, and the activities of AST, ALT, ALP, and GGT. At the same time, it caused a general increase in insulin, albumin, TB, TC, TG, HDL, CAT, SOD, and GSH levels. The histopathological investigation illustrated regeneration of damaged pancreatic beta cells and a clear improvement in the hepatic architecture. Conclusion: The suggested mechanism of action for Ag-NCs in decreasing diabetic complications in the liver involved two pathways; the hypoglycemic activity and the antioxidant role of AgNPs, chitosan, and ascorbic acid.