Studies on Jackfruit-Okra Mucilage-Based Curcumin Mucoadhesive Tablet for Colon Targeted Delivery.

The present work investigates a blend of jack fruit mucilage (JFM) and okra mucilage (OKM) as promising mucoadhesive carriers for colon-specific delivery of a curcumin (CMN)-loaded mucoadhesive tablet (CMT) formulation. Formulation optimization was performed using central composite design (CCD) to further decipher the effect of varying proportions of the mucoadhesive carriers JFM and OKG on response factors such as drug release (% DR) and mucoadhesive strength (MA). The optimized formulation CMT (F14) demonstrated a favorable 54.35% in vitro release of CMN in 12 h with release kinetics resulting from a zero-order anomalous diffusion mechanism and MA of 34.1733 ± 1.26 g. Accelerated stability testing of CMT (F14) confirmed a shelf life of about 4.7 years. In vivo drug targeting studies performed using rabbit models in order to observe transit behavior (colon-specific delivery) of the dosage form were assessed by fluoroscopic images of the GI tract. Taking the results together, the results confirm that the combination of JFM and OKM could be exploited as an ideal mucoadhesive carrier for effective delivery of macromolecules to the colon.

Etiopathophysiological role of the renin-angiotensin-aldosterone system in age-related muscular weakening: RAAS-independent beneficial role of ACE2 in muscle weakness.

Aging is accompanied by major changes in body composition that can negatively affect functional status in older adults, including a progressive decrease in muscle mass, strength, and quality. The prevalence of sarcopenia has varied considerably, depending on the definition used and the population surveyed-a 2014 meta-analysis across several countries found estimates ranging from 1% to 29% for people aged 60 years or older, who live independently. The potentially relevant studies were retrieved from the ScienceDirect/Medline/PubMed/Public library of science/Mendeley/Springer link and Google Scholar. Multiple keywords were used for the literature search both alone and in combination. Some of the important keywords used for literature search were as follows: "Epidemiology of muscle weakness/muscle disorders," "Pathogenesis of RAAS in muscle weakness," "Role of Angiotensin 1-7/ACE-2/Mas R axis in muscle weakness," and "Correction pathophysiology of muscle weakness via ACE2." The renin-angiotensin system (RAAS), a major blood pressure regulatory system, is a candidate mediator that may promote aging-associated muscle weakness. Previously, studies explored the proof concept for RAAS inhibition as a therapeutic target. Furthermore, in RAAS, angiotensin II, and angiotensin-converting enzyme 2 (ACE2) have been reported to induce endoplasmic reticulum (ER) stress via glucose-regulated protein 78/eukaryotic translation initiation factor 2α (eIF2α)/activating transcription factor 4 (ATF4)/CHOP axis in the liver. In addition, other mitochondria and ER physical interactions contribute to skeletal muscle dysfunction. However, very few studies have investigated the relationship between RAAS and ER stress-associated pathophysiological events and ACE2-mediated biological consequences in muscle weakness. Thus, the study has been designed to investigate the RAAS-independent beneficial role of ACE2 in muscle weakness.

Development and optimization of sustained release mucoadhesive composite beads for colon targeting.

The present work investigates a blend of Linum Seed mucilage(LSM) and Hibiscus Leaf gum(HLG) as mucoadhesive carriers for Capecitabine(CPTB) loaded mucoadhesive composite bead formulation (CMB), in an attempt to achieve sustained release of CPTB (BCS Class I drug) in the colon region. Optimization using Box-Behnken Design(BBD) was used to study the effect of quantities of mucoadhesive carriers(LSM,HLG) and enteric polymer pectin (in curing solution) on response factors such as %drug loading (%DL) and %drug release (%DR). CMB prepared by ion-gelation technique showed uniform bead size, spherical surface morphology, maximum drug encapsulation efficiency. The optimized CMB(F18) exhibited maximum %drug loading(28.94%), favorable in vitro drug release of CPTB(54.43%) in 12 h, where, the release kinetics follow zero order non-Fickian diffusion mechanism. CMB's exhibited significantly higher swelling upon exposure to alkaline media than acidic media similarly ex vivo mucoadhesive study also revealed that major fraction of beads were washed off within 2 h in 1.2pH media whereas in 7.4pH alkaline media major portion of the beads remain adhered even after 24 h Moreover accelerated stability testing of CMB(F18) revealed shelf life of about 2.59 years. Hence the study confirms that the combination of LSM&HLG as ideal mucoadhesive carriers and can favorably target highly soluble drugs to the colon region.

Design and development of Albizia stipulata gum based controlled-release matrix tablets in cancer therapeutics.

The present study deals with the development of natural macromolecule gum Albizia stipulata (AS) based novel pharmaceutical excipient for the controlled-release of paracetamol (PC). Central composite design (CCD) two-factor, five-level was used for the optimization of independent variables AS gum and compression force (CF) based on desired response variable drug release (DR) of paracetamol matrix tablets (PCMT). The optimized PCMT was prepared by wet granulation method and screened for pre- and post- compression parameters, and were characterized. The optimized PCMT (F14) formulation showed favorable in vitro release of PC (65%) in 12h, and the release kinetics followed zero order anomalous diffusion mechanism. AS gum exerted significant (p<0.001) anticancer activity with 98.25% inhibition at 2000µg/mL (IC50=179.12µg/mL) against A549 cell line. PC and PCMT showed 78.56% inhibition (IC50 value=856.58µg/mL) and 93.68% inhibition (IC50 value=396.35µg/mL) respectively, symbolizing that the gum remarkably potentiated the anticancer effect of PC in formulation after 24h treatment by inducing apoptosis. This is the first report on A. stipulata gum as a promising biopolymer for drug delivery application in cancer therapeutics.

Effect of formulation variables on rifampicin loaded alginate beads.

The present work investigated the preparation of biodegradable beads with alginate polymer by ionotropic gelation method to improve the control release properties of the antibiotic rifampicin. Ionotropic gelation method was applied to prepare beads using calcium chloride (CaCl2) as cationic component and alginate as an anionic component. In this method, adding 0.5% w/v polyvinyl alcohol (PVA) to sodium alginate (3.0% w/v) and 2% w/v of polyvinyl pyrrolidone (PVP) to the CaCl2 solution were maintained to study the drug-loading and its released characteristics. The results showed that the addition of PVA and PVP significantly improved drug-loading, encapsulation efficiency and release characteristics. This demonstrates that the ionic gelation of alginate molecules offers a flexible and easily controllable process.