Peptic ulcer disease (PUD) is one of the most prevalent gastro intestinal disorder which often leads to painful sores in the stomach lining and intestinal bleeding. Untreated Helicobacter pylori (H. pylori) infection is one of the major reasons for chronic PUD which, if left untreated, may also result in gastric cancer. Treatment of H. pylori is always a challenge to the treating doctor because of the poor bioavailability of the drug at the inner layers of gastric mucosa where the bacteria resides. This results in ineffective therapy and antibiotic resistance. Current treatment regimens available for gastric ulcer and H. pylori infection uses a combination of multiple antimicrobial agents, proton pump inhibitors (PPIs), H2-receptor antagonists, dual therapy, triple therapy, quadruple therapy and sequential therapy. This polypharmacy approach leads to patient noncompliance during long term therapy. Management of H. pylori induced gastric ulcer is a burning issue that necessitates alternative treatment options. Novel formulation strategies such as extended-release gastro retentive drug delivery systems (GRDDS) and nanoformulations have the potential to overcome the current bioavailability challenges. This review discusses the current status of H. pylori treatment, their limitations and the formulation strategies to overcome these shortcomings. Authors propose here an innovative strategy to improve the H. pylori eradication efficiency.
25 January 2024 in Journal of Drug Delivery Science and Technology
The study involved the formulation of cabazitaxel loaded D-alpha-tocopheryl succinate/chitosan conjugate (CSVE) and hyaluronic acid (HA) based redox-responsive nanoparticles crosslinked using 3,3′-dithiodipropionic acid (DTPA). The nanoparticle surface was functionalized with cetuximab (Cmab) to give CSVE/HA/DTPA/Cmab NP for EGFR targeted delivery of the payload. The formulations were subjected to particle analysis, morphological assessment, solid-state characterization, and in vitro drug release studies. The results showed cationic, sub-200 nm sized spherical particles with the glutathione-responsive release of cabazitaxel. In vitro studies revealed a marked decrease in the IC50 value, improved cellular uptake, and a superior apoptotic effect. To determine the in vivo efficacy of the formulation, pharmacokinetic assessment, tumor regression analysis, and survival analysis were performed. The nanoparticles showed improved pharmacokinetic and anti-tumor efficacy compared to free cabazitaxel. The prepared nanoparticles demonstrated immense potential in targeted delivery of the payload for enhanced breast cancer therapy.
Aim: The aim of the present study is to develop a liquid chromatography-mass spectrometry method to measure two important biomarkers of biotin deficiency from dried blood spot samples for effective management of the disorder. Materials & methods: The method was developed on a liquid chromatography-mass spectrometry system using pentafluorophenyl column employing a mobile phase composition of methanol and water in the isocratic mode. A full validation of the method was performed as per relevant guidelines. Results & conclusion: Correlation between the results of dried blood spot and plasma method was evaluated to determine the interconvertibility of the method. The developed method was successfully applied for establishing the reference ranges for these biomarkers in the population of Udupi, a coastal district of South India.
7 November 2024 in International Journal of Applied Pharmaceutics
Objective: Paclitaxel (PTX) is one of the oldest chemotherapeutic agents for cancer treatment. However, PTX is a class IV drug under the Biopharmaceutical Classification System (BCS), and its oral administration is restricted due to its low bioavailability. Complexing PTX with Beta-Cyclodextrin (β-CD) is an option to overcome the low solubility and bioavailability. This study aims to optimize and develop an RP-HPLC analytical method for quantifying PTX from the fabricated β-CD complex. Methods: The HPLC settings were optimized using Design-of-Experiments (DOE) software. The independent variables for the optimization process were buffer ratio, buffer pH, flow rate, and injection volume. The responses were Retention Time (RT), peak area, Tailing Factor (TF), and number of Theoretical Plates (TP) of PTX. The validated method was then used to measure the % entrapment from the PTX-β-CD complex. Results: The developed and optimized RP-HPLC method was validated as per International Council for Harmonisation (ICH) Q2 (R1) guidelines. The developed method showed linearity R2 = 0.999 with a 0.5-20 µg/ml range. The Limit of Detection (LOD) and Limit of Quantification (LOQ) were 95 and 125 ng/ml, respectively. The accuracy and precision for the developed method came under the acceptance criteria. The developed method was used to evaluate the enhancement of solubility of the prepared PTX-β-CD complex. The method was also used in the evaluation of % drug loading, % drug release and stability of the PTX-β-CD complex. The study clearly showed that the solubility of PTX increased from 0 to 1.14±0.53 µg/ml at pH 1.2 and 0 to 3.18±0.61 µg/ml at pH 6.8, respectively. The PTX-β-CD complex showed 73±3.75% drug release in 120 min at pH 1.2 and 87±3.51% at pH 6.8. The developed RP-HPLC method was found to be eco-friendly as per the Analytical Greenness (AGREE) metric approach and software analysis. Conclusion: An eco-friendly RP-HPLC analytical method was successfully developed and optimized for the quantification of PTX from the PTX-β-CD complex.
Deficiency of cofactors for various enzymes can lead to inborn errors of metabolism. These conditions frequently occur as seizures, which lead to permanent brain damage. Newborn screening for biomarkers associated with these disorders can help in early detection and treatment. Our objective was to establish a liquid chromatography mass spectrometry technique for quantifying biomarkers in dried urine spots to detect specific vitamin‐responsive inborn errors metabolism. Biomarkers were extracted from dried urine spots using a methanol:0.1% v/v formic acid solution (75:25) containing an internal standard mixture. Separation was achieved using a Luna PFP column (150 mm × 4.6 mm, 3 µm) under gradient elution conditions. The LC–MS technique was validated as per ICH M10 guidelines. Urine samples from healthy newborns in Udupi district, South India, were analyzed to establish reference values for these biomarkers. The method demonstrated excellent linearity ( R2 > 0.99) with low limits of quantification: 0.1 µg/mL for leucine, isoleucine, valine, proline, hydroxyproline, methylmalonic acid, and 3‐hydroxyisovaleric acid; 0.01 µg/mL for pipecolic acid and α‐aminoadipic semialdehyde; and 0.03 µg/mL for piperideine‐6‐carboxylate. Interconvertibility between urine and dried urine spot assays was observed from the results of the regression and Bland–Altman analyses. Reference intervals for these biomarkers in the Udupi neonatal population were established using the validated dried urine spot method.