Drug Delivery Letters - Volume 13, Issue 4, 2023

Colon targeted medication delivery is a field of study for disorders including colon cancer and inflammatory bowel disease (IBD), with the goal of delivering localised therapy with minimal systemic damage. In recent decades, the global prevalence of colonic problems has increased, demanding more local treatment of colonic disorders, which will lead to the development of more effective and safe pharmaceutical regimens. When developing a formulation for colonic administration, it's critical to consider both the physiological characteristics of the colon and the environment surrounding the disease site (s). The GI tract experiences dynamic changes in motility, fluid volume, enzyme activity, and pH from the stomach to the intestine. The current review focuses on Biodegradable polymers or protein-based microspheres having free-flowing properties and particle size 5200 nm have a variety of advantages over conventional colon targeted drug delivery systems. During drug transit through the GIT, polysaccharides maintain their integrity and inhibit drug release. When it comes into contact with colonic fluid, however, it is attacked by anaerobic microbes, and the imprisoned medication is released. In this review, several methods of microsphere formulation and characterization were investigated along with its in vitro and in vivo study methodology.

The goal of precision medicine is to create treatments for a single person or group of people based on information about their physical condition in the present and the past as well as their exposure to the environment. Precision medicine is now having an impact on how people are treated for their health at different periods of their lives through a variety of applications. Applications of precision medicine can help prevent death, alert patients regarding genetic risks, lower medical expenses, and enhance the quality of life. To determine the risk that a child may inherit an illness, genetic testing is performed before conception. The most severe type of brain cancer is glioblastoma (GBM), commonly referred to as grade IV astrocytoma. Although they can penetrate the brain, GBMs normally do not spread to other organs. One effective kind of treatment for glioblastoma is precision medicine, which is currently being developed. Numerous improvements in diagnosis and therapy have resulted in the healing of many patients without having an impact on their way of life. In terms of diagnosis and treatment, this article compares and contrasts precision technology and traditional therapy. Stem cell treatment, immunotherapy, and combination therapy are all extensively described.

Background: SIM is a poorly water-soluble drug with dissolution-dependent bioavailability. A solid dispersion and self-emulsifying drug delivery system was developed, optimized, and evaluated to improve its bioavailability. The permeability coefficient in rats was determined using the in-situ single-pass intestinal perfusion (SPIP) technique. Further, the permeability coefficient (Peff, humans) was used to calculate the permeability and fraction of SIM bioavailable to humans which have not yet been reported for these formulations.Objective: To estimate and compare various formulations of Simvastatin (SIM) for bioavailable fraction to humans (Fa) as a function of solubility enhancement.Methods: In this study, the preparation and evaluation of SIM formulations i.e., Self-emulsifying drug delivery system (SEDDS) and Solid dispersions (SD) are discussed in brief. An uncomplicated, precise, and accurate HPLC method was validated for simultaneous determination of SIM and phenol red as per ICH guidelines. A comparative in-vitro dissolution test, pharmacokinetic studies, and in-situ SPIP technique in rats were carried out amongst optimized formulations of SIM-SD and SIM-SEDDS, SIM suspension (SIM-SUSP), and SIM marketed preparation (SIM-MP).Results: The HPLC method was successfully validated. In-vitro dissolution test displays that both the SIM formulations i.e., SIM-SEDDS and SIM-SD shows better dissolution rate than SIM-MP and SIM-SUSP. Pharmacokinetic studies revealed that SIM-SEDDS, SIM-SD, and SIM-MP showed significant differences when compared to SIM-SUSP in terms of Cmax, [AUC] 0-∞ at ≤ 0.05. The comparison of permeability coefficient between SIM SEDDS vs. SIM MP and SIM SEDDS vs. SIM SD were non-significant. In contrast, SIM- SUSP vs. all other formulations were significantly different at ≤ 0.05 (employing two-way ANOVA followed by post-Bonferroni Test). Fa for SIM SUSP, an optimized formulation of SIM-SEDDS, SIM-MP, and SIM-SD are 0.353, 0.977, 0.975, and 0.987 respectively. It is revealed that SIM-SEDDS and SIM-SD showed enhanced absorption and the results are confirmed by in-vitro data, pharmacokinetic studies, and In-situ SPIP techniques.Conclusion: The permeability prediction method is a rapid and economical method for screening chemical compounds with the least possible utilization of resources. So, its use can be extended in prime and initial screening prototypes for the evaluation of compounds in the early stages of their formulations.

Background: The second most common cause of mortality by cancer is thought to be colorectal cancer, which is one of the most prevalent tumours in the world. Many health advantages have been linked to curcumin, which is the key component of turmeric. The goal of the current study was to create a colon-targeted microbead method coated with Eudragit S100 to improve curcumin targeting in the colon by speeding up the rate of its dissolution.Methods: The ionotropic gelation process was used to create the formulations. The surface phenomena, bead shape, entrapment effectiveness, drug loading, and in vitro drug release were all assessed for formulations. Moreover, calcium alginate beads with an improved core were enteric coated with Eudragit S100. The polymer concentration and curing duration significantly affected particle size and entrapment effectiveness, respectively.Results: The particle size of the improved formulation was 705 μm, drug entrapment efficiency was 83.56%, drug loading was 28.64%, and in vitro release was 81.66% after 6 hours in phosphate buffer at pH 6.8. After 10 hours, enteric coating with Eudragit S100 of optimized calcium alginate microbeads revealed a 64.09 ¦plusmn; 0.16% drug release. The calculated values of the regression coefficients for the Higuchi, first-order, and zero-order models were 0.9494, 0.8913, and 0.9579, respectively. The 50% inhibitory concentration value was 2.676 based on the percentage of cell viability.Conclusion: To effectively treat colorectal cancer, the enteric-coated calcium alginate microbeads can deliver curcumin selectively to the colon when taken orally.

Background: The development of safe and biocompatible nanoparticles has always been a major concern in nanomedicine applications. Various studies on the size-dependent toxicity of nanoparticles have been reported but are still controversial. The potential of small-sized nanoparticles can be utilized for imaging and diagnostics. However, insufficient toxicity data on these nanoparticles prevents researchers from utilizing their potential in diagnostics. More studies are needed on the toxicity of small-sized nanoparticles to present unanimous report for safe systemic use. The present study aimed to investigate the toxicity concerns of very small-sized AuNPs (2 ¦plusmn; 0.5 nm, 5 ¦plusmn; 1 nm, and 10 ¦plusmn; 2 nm) and provide a platform for their safe in vivo use.Methods: The cellular interactions of these three small-sized AuNPs with regard to cytotoxicity were investigated on hepatocellular carcinoma (HepG2) and epithelial kidney (HEK-293) cell lines. The cytotoxicity investigation of both cell lines was done through MTT assays, PI & DAPI, and cytology. Cellular stress was investigated by Catalase, TBARS, GSH, SOD & ROS parameters. The AuNPs incubated cells were also assessed for immunogenicity by ELISA, protein interaction by BSA, and cellular internalization by TEM (Edax).Results: All three-sized AuNPs were not toxic on cell viability, apoptosis, necrosis, or cytology assessment. No oxidative stress was noted in both cell types in the presence of 2 and 5-nm-sized AuNPs, whereas 10 nm-sized AuNPs showed little oxidative stress. AuNPs of size 2 and 5 nm were immunologically inert, but 10 nm-sized AuNPs elicited interleukin (IL-4 and IL-10) and interferon IFN gamma response. AuNPs of sized 2 nm showed 4 times the adsorption of albumin protein as compared to AuNPs of sized 5 nm. The TEM micrographs and peak of gold in the Edax graph confirmed the presence of AuNPs in cells.Conclusion: Our results are suggestive of utilizing the potential of these three-sized AuNPs safely in preclinical drug delivery applications.

The PT-31 molecule, a potential antipsychotic, has demonstrated promising results when orally administrated to in vivo models. A recent study suggested the genotoxic and mutagenic potential of PT-31 after acute treatment by intraperitoneal route. This study aimed to evaluate PT-31 potential of inducing genotoxic or mutagenic damage after acute oral administration. For that, adult males and females Balb/C mice were treated acutely by oral administration with vehicle or PT-31 in three different doses (10, 20, and 40 mg kg^-1). After 24 hours from PT-31 administration, animals were euthanized for performing the comet and micronucleus assays. None of the tested groups of PT-31 presented a significant increase in damage index and MN frequency. However, they presented the following tendency on damage index: females presented a tendency at 40 mg kg^-1 and males at 20 mg kg^-1. Regarding the MN assay, male mice at the highest dose of 40 mg kg^-1 presented a tendency of increased MN frequency. Also, there was a significant increase in PCE/NCE ratio in male mice. Results suggest that the male mice group presented higher susceptibility to damage. The tendency of increased damage to DNA and MN frequency suggests that the molecule PT-31 may induce reparable damage to DNA, and these DNA strand repairs may have originated from the MN. However, significant genotoxic and mutagenic effects were not observed. This study reinforces the atypical profile of the molecule as much as its safety by oral route administration.