The Emerging Role of Nanosuspensions for Drug Delivery and Stability

: 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.

Non-Clinical investigation of Tuberculosis Drugs - Conjugated Norbornene-Based Nanocarriers Toxic Impacts on Zebrafish

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: To assess the impacts of the nanocarriers on liver cells using 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 was determined using HepG2 cell 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. A noticeable upregulated PXR, CYP3A and cyp2p6 genes was 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.

Nanocrystals- A substantial platform for drug delivery applications.

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 a reservoir or matrix system. 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.

A Short Appraisal on Gold Nanoparticles: Recent Advances and Applications

: Owing to their unique characteristics and diverse surface activities, gold nanoparticles (AuNPs) have been widely used in various fields of biology. The ease with which AuNPs can be functionalized makes it a useful platform for nanobiological assemblies containing oligonucleotides, antibodies, and proteins. AuNPs bioconjugates have also emerged as an interesting candidate for the development of novel biomaterials for the study of biological systems. AuNPs' flexibility has made them valuable in a variety of biomedical applications. The binding of analytes to AuNPs can change the physicochemical features of AuNPs, such as surface plasmon resonance, conductivity, and redox activity, resulting in observable signals in diagnostics. AuNPs can also be used as a therapeutic platform because of their large surface area, which allows for a dense presentation of multifunctional moieties (e.g., drugs and targeting agents). We present a brief summary of green synthesis, characteristics, and applications of gold nanoparticles in this paper, as well as their translational potential.

Antidiabetic Potential of Silver/Chitosan/Ascorbic Acid Nanocomposites

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. Method: 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.

Peptide Functionalised Nanocarriers for Bone Specific Delivery of PTH (1-34) in Osteoporosis

: Osteoporosis represents a major public health burden especially considering the aging population worldwide. Treatment modalities for osteoporosis are classified into two categories based on the effect on bone remodelling: anabolic drugs and antiresorptive drugs. Anabolic drugs are preferred as it stimulates new bone formation. Currently, PTH (1-34) is the only peptide-based drug approved as an anabolic agent for the treatment of osteoporosis by both USFDA as well as EMA. However, its non-specific delivery results in prolonged kidney exposure, causing hypercalcemia. Nanotechnology-based drug delivery systems functionalized by conjugating it with homing moieties, such as peptides, offer an advantage of targeted delivery with reduced off-target effects. Here, we propose an innovative and targeted nanovesicle approach to efficiently deliver PTH (1-34) to the bone surface using peptides as a homing moiety. The proposed innovative delivery approach will augment the specific interaction between the drug and bone surface without producing side effects. This will reduce the off-target effects of PTH (1-34), and at the same time, it will also improve the outcome of anabolic therapy. Therefore, we postulate that the proposed innovative drug delivery approach for PTH (1-34) will establish as a promising therapy for osteoporotic patients, specifically in postmenopausal women who are at greater risk of bone fracture.

Formulation and Evaluation of Liposomal Drug Delivery System for Sulfasalazine

Aim: Aim of the current study is to prepare and characterize sulfasalazine-loaded liposomes to improve the bioavailability of the drug and to lessen the adverse effects of the drug. Background: Diseases like inflammatory bowel disease can be treated by anti-inflammatory agents like “Sulfasalazine,” It can also be used to treat ulcerative colitis and Crohn’s disease. The biological half-life of sulfasalazine is 5-10hr; as in the case of conventional therapy, there is a chance of missing the dose. Therefore, frequent administration of drugs is essential to maintain the desired steady-state level. The side effects are thrombocytopenia, megaloblastic anemia, bone marrow depression, folic acid deficiency, impairment of male fertility (Oligospermia), intestinal nephritis due to 5-ASA, diarrhoea, headache, and skin rashes. The bioavailability of sulfasalazine is 15%. This work was undertaken to enhance bioavailability and decrease the side effects. Objective: The main objective of the study is to improve the solubility of sulfasalazine by formulating a liposomal drug delivery system. The major objective is to develop a liposomal formulation with good stability and the highest entrapment efficiency. Methods: Liposomes were produced by the thin-film hydration method. Nine formulations of liposomes were prepared by varying the concentrations of soya lecithin and cholesterol and changing the drug ratio. The obtained liposomes were characterized for surface morphology, FTIR, particle size, zeta potential, drug content, entrapment efficiency, and in-vitro diffusion studies. Results: Among the nine formulations of liposomes, F3 was found to be the best formulation with an entrapment efficiency of 97.8% and a zeta potential value of -37.2mV. Liposomes followed first-order kinetics with a non-fickian diffusion pathway. Conclusions: Sulfasalazine loaded liposomes were prepared with good stability and the highest entrapment efficiency.

Folate conjugated solid lipid nanoparticle: formulation development, optimization and characterization

Objective: The current paper represents the development, optimization, and characterization of paclitaxel-loaded folate conjugated solid lipid nanoparticles (FA-SLNs). Methods: The ligand (FA-SLNs) conjugated and non-conjugated SLNs (PTX-SLNs) were prepared by hot homogenization method. Both of the formulations (FA-SLNs and PTX-SLNs) were optimized with various parameters i.e. drug loading, stirring time, stirring speed, particle size, and polydispersity index, and characterized. The in-vitro drug release study was performed in different pH environments by using the dialysis bag method. The surface morphology and particle size were determined through scanning electron micorscopy and Transmission Electron Microscopy respectively, The SLNs formulations were also evaluated for the stability study. Result: The particle size of PTX-SLNs and FA-SLNs was determined and found to be 190.1±1.9 and 231.3±2.3 nm respectively. The surface morphology of the SLNs indicates that the prepared formulations are round-shaped and show smooth surfaces. The TEM study indicated that particles were in the range of 100-300 nm. The entrapment efficiency and drug loading capacity of FA-SLNs were found to be 79.42±1.6% and 17.3±1.9%, respectively. In-vitro drug release study data, stated that the optimum drug release was found in an acidic environment at pH 4.0, that showed 94.21% drug release after 16 hours and it proves that optimized formulation FA-SLNs will gave the sustained and better release in tumor tissue that owing acidic environment because of the angiogenesis process. Conclusion: In this research paper, different formulation parameters, found to influence fabrication of drug into Solid lipid nanoparticles, were optimized for high entrapment efficiency and drug loading. The most important parameters were drug:lipid ratio, drug:polymer ratio and lipid: surfactant ratio. Higher in-vitro drug release was observed in pH 4 as compared to the pH 7.4. These result data concludes that FA-SLNs formulation was successfully prepared, optimized and characterized.