NANOSPONGES: AN EVOLUTIONARY TREND FOR TARGETED DRUG DELIVERY

Recent developments in nanotechnology have made the framework for the growth of new nanoscale biomaterials with numerous potential uses in nanomedicine. The nanosponge is a new and emerging technology that can be used to target medicine delivery in a precise and regulated manner. Nanosponge is an important component of advanced medication delivery. It is a specialized assisting system for regulated medication delivery of both lipophilic and hydrophilic medicines in a regulated manner. Effective medication delivery at a specific location allowed for more exact control of release rates and boosted health-care system compliance, but the chemistry having complex shape complicated things. The invention of nanosponges, on the other hand, has provided significant approach to tackling this problem. The technology of Nanosponge has been studied widely for the delivery of drugs for oral, topical, and parental administration. Enzymes, proteins, vaccines, and antibodies can all be delivered effectively using nanosponges. It is more effective for targeted drug delivery systems because it improves solubility, bioavailability, and decreases side effects by releasing the drug at specific site. It has the ability to improve drug solubility and can be manufactured into oral, topical, and parenteral dose forms. This type of carrier system is best for drugs with low bioavailability. Nanosponges can contain both lipophilic and hydrophilic medicines. Nanosponges are extremely permeable, with a high proclivity for ensuring dynamic particles and programmable delivery. This review article discusses nanosponges in general, their advantages & disadvantages, mechanism; factors influence nanosponge, preparation methods, evaluation parameters as well as applications.

Evaluating Organism-Wide Changes in the Metabolome and Microbiome following a Single Dose of Antibiotic

ABSTRACT Antibiotics are a mainstay of modern medicine, but as they kill their target pathogen(s), they often affect the commensal microbiota. Antibiotic-induced microbiome dysbiosis is a growing research focus and health concern, often assessed via analysis of fecal samples. However, such analysis does not inform how antibiotics influence the microbiome across the whole host or how such changes subsequently alter host chemistry. In this study, we investigated the acute (1 day postadministration) and delayed (6 days postadministration) effects of a single parenteral dose of two common antibiotics, ampicillin or vancomycin, on the global metabolome and microbiome of mice across 77 different body sites from 25 different organs. The broader-spectrum agent ampicillin had the greatest impact on the microbiota in the lower gastrointestinal tract (cecum and colon), where microbial diversity is highest. In the metabolome, the greatest effects were seen 1 day posttreatment, and changes in metabolite abundances were not confined to the gut. The local abundance of ampicillin and its metabolites correlated with increased metabolome effect size and a loss of alpha diversity versus control mice. Additionally, small peptides were elevated in the lower gastrointestinal tract of mice 1 day after antibiotic treatment. While a single parenteral dose of antibiotic did not drastically alter the microbiome, nevertheless, changes in the metabolome were observed both within and outside the gut. This study provides a framework for how whole-organism -omics approaches can be employed to understand the impact of antibiotics on the entire host. IMPORTANCE We are just beginning to understand the unintended effects of antibiotics on our microbiomes and health. In this study, we aimed to define an approach by which one could obtain a comprehensive picture of (i) how antibiotics spatiotemporally impact commensal microbes throughout the gut and (ii) how these changes influence host chemistry throughout the body. We found that just a single dose of antibiotic altered host chemistry in a variety of organs and that microbiome alterations were not uniform throughout the gut. As technological advances increase the feasibility of whole-organism studies, we argue that using these approaches can provide further insight on both the wide-ranging effects of antibiotics on health and how to restore microbial communities to mitigate these effects.

Intrathecal Methotrexate Containing the Preservative Benzyl Alcohol Erroneously Administered in Pediatric Leukemia Patients: Clinical Course and Preventive Process

Administration of intrathecal chemotherapy for leukemia is a common procedure in pediatric oncology. The direct delivery of drug into the cerebral spinal fluid requires that no preservative be used. Preserved drugs administered in error can result in significant neurotoxicity. A case series is described where preservative-containing methotrexate was incidentally administered intrathecally. All patients were treated at Children's Hospitals and Clinics of Minnesota. Medical records of the patients affected were reviewed and abstracted for this report. Four children with acute lymphoblastic leukemia received 1 dose of intrathecal methotrexate that contained 0.07% benzyl alcohol in January 2019. Overall, minimal to no symptoms were seen after dosing. The error was traced to a drug shortage in which benzyl alcohol–containing methotrexate was obtained and incorrectly stocked. A novel replacement drug procurement process was developed within our institution. The process includes sequestered queues where a drug awaits evaluation and independent double check of entry accuracy in the electronic health record and pharmacy parenteral dose preparation software prior to release and use. In contrast to IV administration, intrathecal benzyl alcohol at concentrations ≥ 0.9% can cause significant neurotoxicity. Although minimal, if any, neurotoxicity was seen in patients who received a 10-fold lower concentration of benzyl alcohol than previously associated with complications, all institutions should recognize the potential for this error and implement similar safety precautions to ensure that this type of error will not occur.

THE IMPACT OF DIFFERENT REGIMENS OF VITAMIN D3 ON GLUCOSE HOMEOSTASIS IN TYPE 2 DIABETIC PATIENTS

Objective: Vitamin D has a role in the regulation of pancreatic β-cell function and insulin sensitivity. Accordingly, Vitamin D deficiency is considered to be a risk factor for the development of type 2 diabetes mellitus (T2DM) and its complications. Therefore, the aim of the study was to assess and compare the effect of different regimens of Vitamin D3 on glucose homeostasis in patients with T2DM. Methods: The study included 80 patients with T2DM taking oral antidiabetic drugs. The patients were randomized to receive antidiabetic drugs alone or with different regimens of Vitamin D3 for 3 months. Vitamin D3-treated patients were supplemented by either daily oral 4000 IU Vitamin D3, weekly oral 50,000 IU Vitamin D3, or a single parenteral dose of 300,000 IU Vitamin D3. In addition to the assessment of patient characteristics, laboratory measurements of serum creatinine, blood urea, total and ionized calcium, serum phosphorus, fasting blood glucose, fasting serum insulin, homeostasis model assessment of insulin resistance, hemoglobin A1c, and 25(OH) Vitamin D levels were measured at the beginning and after 3 months. Results: After 3 months, the increased Vitamin D levels resulting from the daily and weekly oral doses of Vitamin D3 caused a significant decrease in metabolic parameters, whereas the parenteral dose demonstrated a non-significant decrease. Conclusion: Oral daily and weekly doses of Vitamin D3 could improve glucose homeostasis equally in patients with T2DM and better than a single parenteral dose of Vitamin D3.

POSSIBILITY OF ORALLY ADMINISTERED L-LYSINE-A-OXIDASE INTERNALIZATION IN THE MODEL OF ISOLATED CUT OF RAT SMALL INTESTINE

Enzyme L-lysine а-oxidase (LO) exhibits significant antitumor effects by parenteral administration and is promising for clinical trials, particularly in the case of colorectal cancer. The fungi Trichoderma cf.aureoviride Rifai VKM F-4268D is a source of LO. Since there is evidence in the literature of oral use of proteins for therapeutic purposes, it seemed promising to investigate the possibility of such administration route for LO. The goal of the work was to determine the ability of LO to be internalized by the rat small intestine. LO was labeled by Ac-ridinium (LO-Acridinium). Experiments were performed on the rat model using isolated inverted segments of small intestine. The inverted segments were immersed into incubation medium, containing LO-Acridinium. After 30 minutes the samples were taken from the incubation medium and from the intestine segments and relative luminescence was determined by standard flash luminescence method. The amount of absorbed LO-Ac-ridinium was estimated to be 11% for the entire length of the small rat intestine. Based on the optimal total parenteral dose of 400 U/kg for mice the total dose when administered orally was estimated as 4000 U/kg. The absorption of LO through the wall of the rat small intestine was quantitatively characterized, the possibility of its oral administration was proved, and the oral therapeutic dose for mice was estimated.

Intravenous Pantoprazole: A New Tool for Acutely Ill Patients Who Require Acid Suppression

Until now, oral proton pump inhibitors have not been available as parenteral therapy in the acute care setting. Pantoprazole is the first parenteral proton pump inhibitor to become available in Canada. This agent is superior to the parenteral histamine2receptor antagonists with respect to acid suppressive effects and is not associated with tolerance development. Another advantage over the histamine2receptor antagonists is that pantoprazole does not require dosage adjustment in patients with renal impairment. Dosage adjustments are also not required for elderly patients or those with hepatic impairment when the drug is used at the usual dose for a limited period of time. Contrary to intravenous cimetidine and ranitidine, which have negative inotropic and chronotropic effects, intravenous pantoprazole is well tolerated and has no significant effect on heart rate, contractility or blood pressure. The lack of drug interactions for this agent also simplifies its use, especially in patients who may require multiple drugs during hospitalization. Parenteral pantoprazole is effective in the treatment of reflux esophagitis. It is also promising for the treatment of upper gastrointestinal bleeding and in the perioperative care of patients with Zollinger-Ellison syndrome, but further research in these areas is necessary. Once the patient is able to tolerate oral medications, parenteral therapy can be easily converted to oral therapy using an oral dose that was equivalent to the parenteral dose (ie, 40 mg given intravenously is equivalent to 40 mg given orally).

Excretion of ciprofloxacin into the large bowel of the rabbit.

The intestinal elimination of ciprofloxacin in the large bowel was studied in a rabbit model. Segments from the cecum, colon, and sigmoid colon along with their intact blood vessels were isolated and perfused, and their contents were collected over a 90-min period following the administration of a single parenteral dose of 27 mg of ciprofloxacin per kg of body weight. The elimination rates of ciprofloxacin were 0.126 +/- 0.084 micrograms.min-1.cm-2 in the cecum and 0.264 +/- 0.126, 0.11 +/- 0.07, and 0.21 +/- 0.141 micrograms.min-1.cm-2 in the proximal colon, distal colon, and sigmoid colon, respectively. The calculated fraction of ciprofloxacin eliminated in the large bowel was 3% of the parenteral dose administered. The elimination pattern of ciprofloxacin in the large bowel may explain the unusual activity of this fluoroquinolone in modifying the colonic flora.