scholarly journals An ingestible self-orienting system for oral delivery of macromolecules

Science ◽  
2019 ◽  
Vol 363 (6427) ◽  
pp. 611-615 ◽  
Author(s):  
Alex Abramson ◽  
Ester Caffarel-Salvador ◽  
Minsoo Khang ◽  
David Dellal ◽  
David Silverstein ◽  
...  
Keyword(s):  
Oral Delivery ◽  
Active Pharmaceutical Ingredient ◽  
Drug Uptake ◽  
In Vivo Studies ◽  
Gi Tract ◽  
Pharmaceutical Ingredients ◽  
Model Drug ◽  
Poor Absorption ◽  
Systemic Drug

Biomacromolecules have transformed our capacity to effectively treat diseases; however, their rapid degradation and poor absorption in the gastrointestinal (GI) tract generally limit their administration to parenteral routes. An oral biologic delivery system must aid in both localization and permeation to achieve systemic drug uptake. Inspired by the leopard tortoise’s ability to passively reorient, we developed an ingestible self-orienting millimeter-scale applicator (SOMA) that autonomously positions itself to engage with GI tissue. It then deploys milliposts fabricated from active pharmaceutical ingredients directly through the gastric mucosa while avoiding perforation. We conducted in vivo studies in rats and swine that support the applicator’s safety and, using insulin as a model drug, demonstrated that the SOMA delivers active pharmaceutical ingredient plasma levels comparable to those achieved with subcutaneous millipost administration.

Biopharmaceutical and Preclinical Studies of Zaleplon as Semisolid Dispersions with Self-emulsifying Lipid Surfactants for Oral Delivery

1970 ◽  
Vol 9 (1) ◽  
pp. 3102-3111
Author(s):  
Narendar Dudhipala ◽  
Arjun Narala ◽  
Dinesh Suram ◽  
Karthik Yadav Janga
Keyword(s):  
Oral Delivery ◽  
Molecular State ◽  
In Vivo Studies ◽  
In Vitro Dissolution ◽  
Content Uniformity ◽  
Phase Solubility ◽  
Microscopic Studies ◽  
Pure Drug

The objective of this present study is to develop a semisolid dispersion (SSD) of zaleplon with the aid of self-emulsifying lipid based amphiphilic carriers (TPGS E or Gelucire 44/14) addressing the poor solubility of this drug. A linear relationship between the solubility of drug with respect to increase in the concentration of lipid surfactant in aqueous medium resulting in AL type phase diagram was observed from phase solubility studies. Fusion method was employed to obtain semisolid dispersions (SSD) of zaleplon which showed high content uniformity of drug. The absence of chemical interactions between the pure drug, excipients and formulations were conferred by Fourier transmission infrared spectroscopic examinations. The photographic images from polarized optical microscopic studies revealed the change in crystalline form of drug to amorphous or molecular state. The superior dissolution parameters of zaleplon from SSD over pure crystalline drug interpreted from in vitro dissolution studies envisage the ability of these lipid surfactants as solubility enhancers. Further, the caliber of TPGS E or Gelucire 44/14 in encouraging the GI absorption of drug was evident with the higher human effective permeability coefficient and fraction oral dose of drug absorbed from SSD in situ intestinal permeation study. In conclusion, in vivo studies in Wister rats demonstrated an improvement in the oral bioavailability of zaleplon from SSD over control pure drug suspension suggesting the competence of Gelucire 44/14 and TPGS E as conscientious carriers to augment the dissolution rate limited bioavailability of this active

Oil based nanocarrier for improved oral delivery of silymarin: In vitro and in vivo studies

2011 ◽  
Vol 413 (1-2) ◽  
pp. 245-253 ◽  
Author(s):  
Rabea Parveen ◽  
Sanjula Baboota ◽  
Javed Ali ◽  
Alka Ahuja ◽  
Suruchi S. Vasudev ◽  
...  
Keyword(s):  
Oral Delivery ◽  
In Vivo Studies

scholarly journals A Review of the Role of Neurotensin and Its Receptors in Colorectal Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Shengyang Qiu ◽  
Gianluca Pellino ◽  
Francesca Fiorentino ◽  
Shahnawaz Rasheed ◽  
Ara Darzi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Animal Studies ◽  
In Vivo Studies ◽  
Signalling Pathways ◽  
Diagnostic Biomarker ◽  
Gi Tract ◽  
Cellular Receptors

Neurotensin (NTS) is a physiologically occurring hormone which affects the function of the gastrointestinal (GI) tract. In recent years, NTS, acting through its cellular receptors (NTSR), has been implicated in the carcinogenesis of several cancers. In colorectal cancer (CRC), a significant body of evidence, from in vitro and in vivo studies, is available which elucidates the molecular biology of NTS/NTSR signalling and the resultant growth of CRC cells. There is growing clinical data from human studies which corroborate the role NTS/NTSR plays in the development of human CRC. Furthermore, blockade and modulation of the NTS/NTSR signalling pathways appears to reduce CRC growth in cell cultures and animal studies. Lastly, NTS/NTSR also shows potential of being utilised as a diagnostic biomarker for cancers as well as targets for functional imaging. We summarise the existing evidence and understanding of the role of NTS and its receptors in CRC.

Nanocarrier based formulation of Thymoquinone improves oral delivery: Stability assessment, in vitro and in vivo studies

2013 ◽  
Vol 102 ◽  
pp. 822-832 ◽  
Author(s):  
Anjali Singh ◽  
Iqbal Ahmad ◽  
Sohail Akhter ◽  
Gaurav K. Jain ◽  
Zeenat Iqbal ◽  
...  
Keyword(s):  
Oral Delivery ◽  
In Vivo Studies ◽  
Stability Assessment

Natural Furanocoumarin as Potential Oral Absorption Enhancer

2019 ◽  
Vol 819 ◽  
pp. 63-69
Author(s):  
May Phyu Thein Maw ◽  
Panadda Phattanawasin ◽  
Uthai Sotanaphun ◽  
Nusara Piyapolrungroj
Keyword(s):  
Oral Delivery ◽  
Oral Absorption ◽  
The Body ◽  
Dual Inhibitor ◽  
Active Efflux ◽  
Intestinal Membrane ◽  
Efflux Mechanism ◽  
Uptake Studies ◽  
Poor Absorption

Bioavailability of orally administered drugs can be influenced by many factors. Poor drug absorption across the intestinal membrane is one of the factors that contribute to low bioavailability of drugs. It has been suggested that the metabolism/active efflux in the small intestine is involved in the poor absorption of many drugs. Intestinal CYP3A4 and P-gp work coordinately to reduce the intracellular concentration of drugs. Recently, bioenhancers have been identified and extensively studied. The aim of this study was to evaluate natural furanocoumarins found in juices of common lime and kaffir lime as the potential enhancers for oral delivery by means of modulating CYP3A4 and/or P-gp activities. The role of isolated furanocoumarins on CYP3A4 was assessed by testosterone 6β-hydroxylation reaction, while the effect on P-gp was investigated using R123 and CAM uptake studies in Caco-2, as well as LLC-PK1 and LLC-GA5-Col300. In the present study, we demonstrated that isopimpinellin isolated from common lime is the best CYP3A4 inhibitor among 4 isolated furanocoumarins, implying that isopimpinellin would possibly act as a bioenhancer by inhibiting pre-systemic metabolism. 6’,7’-Dihydroxybergamottin found in kaffir lime is a dual inhibitor of CYP3A4 and P-gp, suggest that it could potentially be used as a bioenhancer by inhibiting both pre-systemic metabolism and efflux mechanism. However, in vivo study should be further conducted to confirm these effects in the body.

In-situ Intestinal Absorption and Pharmacokinetic Investigations of Carvedilol Loaded Supersaturated Self-emulsifying Drug System

2020 ◽  
Vol 8 (3) ◽  
pp. 207-224
Author(s):  
Vamshi M. Krishna ◽  
Vijaya B. Kumar ◽  
Narendar Dudhipala
Keyword(s):  
Oral Administration ◽  
Oral Delivery ◽  
In Vivo Studies ◽  
Absolute Bioavailability ◽  
Delivery Vehicle ◽  
Biorelevant Dissolution ◽  
Alternative Delivery ◽  
Biorelevant Dissolution Media ◽  
Sem Studies

Background: Carvedilol (CD), a non-selective beta-blocker, is indicated for the management of mild to moderate congestive heart failure. After oral administration, CD is rapidly absorbed with an absolute bioavailability of 18-25% because of low solubility and extensive first-pass metabolism. Objective: The present investigation focused on enhanced oral delivery of CD using supersaturated self-emulsifying drug delivery (SEDDS) system. Methods: Optimized SEDDS consisted of a blend of Oleic acid and Labrafil-M2125 as an oil-phase, Cremophor-RH40, polyethylene glycol-400 and HPMC-E5 as a surfactant, co-surfactant and supersaturation promoter respectively. Formulations were characterized for physical characteristics, invitro release in simulated and biorelevant dissolution media, intestinal permeability and bioavailability studies in Wistar rats. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM) studies were used to confirm the crystalline nature and shape of the optimized formulation. Results: DSC and XRD, SEM studies showed that the drug was in amorphous form, and droplets were spherical in shape. Dissolution studies clearly showed distinct CD release in compendial and biorelevant dissolution media. The results from permeability and in-vivo studies depicted 2.2-folds and 3.2-folds increase in permeability and bioavailability, respectively from supersaturated SEDDS in comparison with control. Conclusions: The results conclusively confirmed that the SEDDS formulation could be considered as a new alternative delivery vehicle for the oral supply of CD. Lay Summary: Carvedilol (CD) is a non-selective antihypertensive drug with poor oral bioavailability. Previously, various lipid delivery systems were reported with enhanced oral delivery. We developed suprsaturable SEDDS formulation with immediate onset of action. SEDDS formulation was developed and optimized as per the established protocols. The optimized SEDDS formulation was stable over three months and converted to solid and supersaturated SEDDS. The results from permeability and in-vivo studies demonstrated an enhancement in permeability and bioavailability from supersaturated SEDDS in comparison with control. The results conclusively confirmed that the SEDDS formulation could be considered as a new alternative delivery vehicle for the oral administration of CD.

scholarly journals In vivo Studies for Drug Development via Oral Delivery: Challenges, Animal Models and Techniques

2017 ◽  
Vol 08 (09) ◽  
Author(s):  
Katherine Brake ◽  
Ashwini Gumireddy ◽  
Amit Tiwari ◽  
Harsh Chauhan ◽  
Dunesh Kumari
Keyword(s):  
Animal Models ◽  
Drug Development ◽  
Oral Delivery ◽  
In Vivo Studies

scholarly journals Determining the Polymer Threshold Amount for Achieving Robust Drug Release from HPMC and HPC Matrix Tablets Containing a High-Dose BCS Class I Model Drug: In Vitro and In Vivo Studies

2014 ◽  
Vol 16 (2) ◽  
pp. 398-406 ◽  
Author(s):  
Uroš Klančar ◽  
Saša Baumgartner ◽  
Igor Legen ◽  
Polona Smrdel ◽  
Nataša Jeraj Kampuš ◽  
...  
Keyword(s):  
Drug Release ◽  
Matrix Tablets ◽  
Class I ◽  
In Vivo Studies ◽  
High Dose ◽  
Model Drug ◽  
Threshold Amount
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