Effect of Short‐, Medium‐, and Long‐Chain Fatty Acid‐Based Vehicles on the Absolute Oral Bioavailability and Intestinal Lymphatic Transport of Halofantrine and Assessment of Mass Balance in Lymph‐Cannulated and Non‐cannulated Rats

Caliph, Suzanne Mary; Charman, William N.; Porter, Christopher John

doi:10.1002/1520-6017(200008)89:8<1073::aid-jps12>3.0.co;2-v

Cited by 266 publications

(169 citation statements)

References 27 publications

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“…Mgf, itself were found to be nontoxic to Caco-2 cells, and is in consonance with the literature findings (Caliph et al, 2000). For improved understanding, the control cells at all the time points have been assumed as 100% and the cell viability for tested formulations has been calculated accordingly (Coker et al, 2012;Cheah et al, 2014).…”

Section: Cell Viability Assaysupporting

confidence: 72%

Enhancing biopharmaceutical attributes of phospholipid complex-loaded nanostructured lipidic carriers of mangiferin: Systematic development, characterization and evaluation

Khurana

Bansal

Beg

et al. 2017

International Journal of Pharmaceutics

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Mangiferin (Mgf), largely expressed out from the leaves and stem bark of Mango, is a potent antioxidant. However, its in vivo activity gets tremendously reduced owing to poor aqueous solubility and inconsistent gastrointestinal absorption, high hepatic first-pass metabolism and high P-gp efflux. The current research work, therefore, was undertaken to overcome the biopharmaceutical hiccups by developing the Mgfphospholipid complex (PLCs) loaded in nanostructured lipidic carriers (NLCs). The PLCs and NLCs were prepared using refluxing, solvent evaporation and hot emulsification technique, respectively with various molar ratios of Mgf and Phospholipon 90 G, i.e., 1:1; 1:2; and 1:3. The complex was evaluated for various physicochemical parameters like drug content (96.57%), aqueous solubility (25-fold improved) and oil-water partition coefficient (10-fold enhanced). Diverse studies on the prepared complex using FTIR, DSC, PXRD and SEM studies ratified the formation of PLCs at 1:1 ratio. The PLCs were further incorporated onto NLCs, which were systematically optimized employing a face centered cubic design (FCCD), while evaluating for particle size, zeta potential, encapsulation efficiency and in vitro drug release as the CQAs. Caco-2 cell line indicated insignificant cytotoxicity, and P-gp efflux, bi-directional permeability model and in situ perfusion studies specified enhanced intestinal permeation parameters. In vivo pharmacokinetic studies revealed notable increase in the values of Cmax (4.7-fold) and AUC (2.1-fold), respectively, from PLCs-loaded NLCs vis-à-vis Mgf solution. In a nutshell, the promising results observed from the present research work signified boosted biopharmaceutical potential of the optimized PLCs-loaded NLCs for potentially augmenting the therapeutic efficacy of Mgf.

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Section: Cell Viability Assaysupporting

confidence: 72%

Enhancing biopharmaceutical attributes of phospholipid complex-loaded nanostructured lipidic carriers of mangiferin: Systematic development, characterization and evaluation

Khurana

Bansal

Beg

et al. 2017

International Journal of Pharmaceutics

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“…2 Lymphatic transport is thought to make a significant contribution to absorption from the intestine as it circumvents the hepatic first-pass effect. 13,14 Recently, Holm et al showed that halofantrine is also transported by the lymphatic system in dogs when administered in long-chain triglyceride-based self-ME drug delivery systems (SMEDDS) formulations. 15 There are numerous other examples in the literature demonstrating the enhanced absorption of drugs through the lymphatic system when using MEs.…”

mentioning

confidence: 99%

“…Previous data suggest that lipids play an important role in the lymphatic transport of lipid-based formulations. 13,17 These results might confirm the transport of MEs through the lymph, but the extent of the contribution of M-cells to this lymphatic transport is still unknown. The primary advantage of intestinal lymphatic drug transport is that drugs absorbed via the intestinal lymphatic system are protected from hepatic first-pass metabolism because the mesenteric lymph, in contrast to the portal blood, enters the systemic circulation directly without first passing through the liver.…”

mentioning

confidence: 99%

Mechanisms of microemulsion enhancing the oral bioavailability of puerarin: comparison between oil-in-water and water-in-oil microemulsions using the single-pass intestinal perfusion method and a chylomicron flow blocking approach

Tang¹,

Hu²,

Liao³

et al. 2013

IJN

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The purpose of the present work was to determine the mechanisms by which microemulsions (MEs) enhance the oral bioavailability of puerarin. The in situ perfusion method was used in rats to study the absorption mechanisms of an oil-in-water (O/W) microemulsion (O/W-ME) and a water-in-oil (W/O) microemulsion (W/O-ME). The possibility of lymphatic transport of the MEs was investigated using a chylomicron flow blocking approach. The results for the absorption mechanisms in the stomach and intestines indicated that the absorption characteristics of the O/W-ME and W/O-ME depend on the segment. The W/O-ME had higher internal membrane permeability than the O/W-ME. The results of the lymphatic transport analyses showed that both the O/W-ME and W/O-ME underwent lymphatic transport and that this pathway was a major contributor to the oral bioavailability of MEs. Furthermore, the type of ME can significantly affect the absorption of puerarin through the lymphatic system due to the oil content and the form of the microemulsion after oral administration. In conclusion, these data indicate that microemulsions are an effective and promising delivery system to enhance the oral bioavailability of poorly water-soluble drugs.

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“…The animals were anesthetized for the duration of the surgeries by intraperitoneal injection of 2% pentobarbital sodium salt (2.5 mL/kg), and additional injections were given if required. The mesenteric lymph duct was cannulated in accordance with a previously described method (Caliph et al, 2000) with some modification. A two-part cannula, consisting of a 3-cm-long silicone tube connected to an 8-cm-long polyethylene tube (PE50), was inserted into the mesenteric lymph duct and secured with medical adhesive bandage.…”

Section: Surgical Proceduresmentioning

confidence: 65%

Effects of lipid vehicle and P-glycoprotein inhibition on the mesenteric lymphatic transport of paclitaxel in unconscious, lymph duct-cannulated rats

Cai

Deng

et al. 2014

Drug Delivery

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The present study examined the effects of lipid vehicle and intestinally based efflux processes on intestinal lymphatic transport of paclitaxel (PTX) in the mesenteric lymph duct-cannulated anesthetized rat model. PTX solution alone, PTX solution pretreated with the P-glycoprotein (P-gp) inhibitor verapamil and/or PTX and a 2:1 (w/w) mixture of linoleic acid:glycerol monooleate were administered intraduodenally to anesthetized rats. Coadministration of a mixture of linoleic acid-monoolein significantly increased the extent of intestinal lymphatic transport of PTX, but it had little impact on the absolute oral bioavailability of PTX. In contrast, pretreatment with verapamil increased both the extent of lymphatic transport (3.5-fold) and absolute oral bioavailability (1.8-fold). Further increase in the lymphatic transport (6.5-fold) and absolute oral bioavailability (1.8-fold) was achieved by the combination of pretreatment with verapamil and coadministration with the linoleic acid-monoolein mixture. These data indicate that the application of lipid vehicle holds promise for selectively targeted lymphatic delivery of PTX. P-gp inhibition can result in both increased intestinal lymphatic levels and absolute oral bioavailability of PTX.

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Effect of Short‐, Medium‐, and Long‐Chain Fatty Acid‐Based Vehicles on the Absolute Oral Bioavailability and Intestinal Lymphatic Transport of Halofantrine and Assessment of Mass Balance in Lymph‐Cannulated and Non‐cannulated Rats

Cited by 266 publications

References 27 publications

Enhancing biopharmaceutical attributes of phospholipid complex-loaded nanostructured lipidic carriers of mangiferin: Systematic development, characterization and evaluation

Enhancing biopharmaceutical attributes of phospholipid complex-loaded nanostructured lipidic carriers of mangiferin: Systematic development, characterization and evaluation

Mechanisms of microemulsion enhancing the oral bioavailability of puerarin: comparison between oil-in-water and water-in-oil microemulsions using the single-pass intestinal perfusion method and a chylomicron flow blocking approach

Effects of lipid vehicle and P-glycoprotein inhibition on the mesenteric lymphatic transport of paclitaxel in unconscious, lymph duct-cannulated rats

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