Case studies of enhanced pharmacodynamic activity of poorly oral bioavailable drugs via solid lipid nanoparticles

Solid lipid nanoparticles (SLNs) considered as an alternative vehicle for the enhanced oral absorption of drugs, and also to enhance therapeutic effectiveness after oral administration. Pharmacodynamic activity of drug is mainly describes the pharmacological and therapeutic activity of drug to the biological system. Lipid nanoparticles especially SLNs made of physiological inert lipid molecules and helps the lymphatic transport. Numerous literatures is available on the effect of SLNs and other colloidal carrier systems on the pharmacokinetic activity of poorly bioavailable drugs, to improve their oral absorption and also respective mechanisms for the improved oral bioavailability. However, very few literatures is reported on the pharmacodynamic activity and the effect of dose on the pharmacodynamic activity. Therefore, the current review is mainly dealing with the effect of SLNs on the pharmacodynamic activity discussed. Keywords: Oral absorption, solid lipid nanoparticles, lymphatic transport, pharmacokinetics, pharmacodynamics.

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Influence of Solid Lipid Nanoparticles on Pharmaco-dynamic Activity of Poorly Oral Bioavailable Drugs

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2019.13.4.2 ◽

2020 ◽

Vol 13 (4) ◽

pp. 4979-4983

Author(s):

Narendar Dudhipala

Keyword(s):

Solid Lipid Nanoparticles ◽

Oral Absorption ◽

Lipid Nanoparticles ◽

Lymphatic Transport ◽

Pharmacokinetic Parameters ◽

Dynamic Activity ◽

Solid Lipid ◽

Drug Classes ◽

Colloidal Carrier

In the recent scenario, lipid nanoparticles gain much attention on the oral absorption of drugs to enhance therapeutic effectiveness after oral administration. Pharmacodynamic activity of drug mainly describes the pharmacological and therapeutic activity of drug to the biological system. Lipid nanoparticles especially solid lipid nanoparticles are made of physiological inert lipid molecules and promotes the lymphatic transport. Abundant literature is available on the effect of lipid nanoparticles and other colloidal carrier systems on the pharmacokinetic parameters of poorly bioavailable drugs, to improve their oral absorption and also respective mechanisms for the improved oral bioavailability. However, little literature is reported on the pharmacodynamic activity and the effect of dose on the pharmacodynamic activity. It is of paramount importance to assess the influence of lipid nanoparticles on pharmacotherapeutic actions of specific drug classes. Therefore, current review is mainly focused on the role of solid lipid nanoparticles on the pharmacodynamic action and advantages of the developed delivery systems with respect to pharmacodynamic activity.

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ChemInform Abstract: Solid Lipid Nanoparticles: Colloidal Carrier Systems for Drug Delivery

ChemInform ◽

10.1002/chin.201202274 ◽

2011 ◽

Vol 43 (2) ◽

pp. no-no ◽

Cited By ~ 7

Author(s):

G. Swathi ◽

N. L. Prasanthi ◽

S. S. Manikiran ◽

N. Ramarao

Keyword(s):

Drug Delivery ◽

Solid Lipid Nanoparticles ◽

Lipid Nanoparticles ◽

Solid Lipid ◽

Colloidal Carrier ◽

Carrier Systems

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Factorial Design Studies and Biopharmaceutical Evaluation of Simvastatin Loaded Solid Lipid Nanoparticles for Improving the Oral Bioavailability

ISRN Nanotechnology ◽

10.1155/2014/951016 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 10

Author(s):

Kovoru Krishnam Raju ◽

Beeravelli Sudhakar ◽

Kolapalli Venkata Ramana Murthy

Keyword(s):

Solid Lipid Nanoparticles ◽

Oral Bioavailability ◽

Competitive Inhibition ◽

Polymeric Nanoparticles ◽

Analytical Techniques ◽

Lipid Nanoparticles ◽

Lymphatic Transport ◽

Solid Lipid ◽

Reductase Inhibitors ◽

Coa Reductase

Statins are HMG-CoA reductase inhibitors, which lower the cholesterol level through reversible and competitive inhibition; they are involved in the biosynthesis of cholesterol and other sterols. Simvastatin exhibits poor oral bioavailability (<5%) and undergoes extensive microsomal metabolism by CYP enzymes. CYP3A4 is the major metabolizing enzyme that metabolizes lactone form of simvastatin and significantly lowers intestinal uptake. The hydrophobic properties of simvastatin prevent complete dissolution of the drug in the intestinal fluid which also contributes to its lower bioavailability. SLNs are alternative carrier system to polymeric nanoparticles. SLNs are in submicron size range (1–1000 nm). To overcome the hepatic first pass metabolism and to enhance the bioavailability, intestinal lymphatic transport of drugs can be exploited. In the present study, attempt has been made to prepare solid lipid nanoparticles of simvastatin to improve the bioavailability. SLNs of simvastatin were prepared with Trimyristin by hot homogenization followed by ultrasonication method. The SLNs were characterized for various physicochemical properties and analytical techniques like PXRD, DSC to study thermal nature and morphology of formulation and excipients. Promising results of the study indicated the applicability of simvastatin solid lipid nanoparticles as potential tools for improvement of bioavailability of poorly soluble drugs.

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Preparation and Characterization of Loperamide-Loaded Dynasan 114 Solid Lipid Nanoparticles for Increased Oral Absorption In the Treatment of Diarrhea

Frontiers in Pharmacology ◽

10.3389/fphar.2016.00332 ◽

2016 ◽

Vol 7 ◽

Cited By ~ 4

Author(s):

Lili Wei ◽

Yunfang Yang ◽

Kun Shi ◽

Jun Wu ◽

Wei Zhao ◽

...

Keyword(s):

Solid Lipid Nanoparticles ◽

Oral Absorption ◽

Lipid Nanoparticles ◽

Solid Lipid

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Solid Lipid Nanoparticles as Formulative Strategy to Increase Oral Permeation of a Molecule Active in Multidrug-Resistant Tuberculosis Management

Pharmaceutics ◽

10.3390/pharmaceutics12121132 ◽

2020 ◽

Vol 12 (12) ◽

pp. 1132

Author(s):

Antonella Obinu ◽

Elena Piera Porcu ◽

Sandra Piras ◽

Roberta Ibba ◽

Antonio Carta ◽

...

Keyword(s):

Solid Lipid Nanoparticles ◽

Oral Absorption ◽

Antitubercular Activity ◽

Multidrug Resistant ◽

Lipid Nanoparticles ◽

Particle Size Range ◽

Solid Lipid ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis

The role of mycobacterial efflux pumps in drug-resistant tuberculosis has been widely reported. Recently, a new compound, named SS13, has been synthesized, and its activity as a potential efflux inhibitor has been demonstrated. In this work, the chemical–physical properties of the SS13 were investigated; furthermore, a formulative study aimed to develop a formulation suitable for oral administration was performed. SS13 shows nonintrinsic antitubercular activity, but it increases the antitubercular activity of all the tested drugs on several strains. SS13 is insoluble in different simulated gastrointestinal media; thus, its oral absorption could be limited. Solid lipid nanoparticles (SLNs) were, therefore, developed by using two different lipids, Witepsol and/or Gelucire. Nanoparticles, having a particle size (range of 200–450 nm with regards to the formulation composition) suitable for intestinal absorption, are able to load SS13 and to improve its permeation through the intestinal mucosa compared to the pure compound. The cytotoxicity is influenced by the concentration of nanoparticles administered. These promising results support the potential application of these nanocarriers for increasing the oral permeation of SS13 in multidrug-resistant tuberculosis management.

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Quality by Design Approach for Development and Characterisation of Solid Lipid Nanoparticles of Quetiapine Fumarate

Current Computer - Aided Drug Design ◽

10.2174/1573409915666190722122827 ◽

2020 ◽

Vol 16 (1) ◽

pp. 73-91 ◽

Cited By ~ 2

Author(s):

Shweta Agarwal ◽

Rayasa S. Ramachandra Murthy ◽

Sasidharan Leelakumari Harikumar ◽

Rajeev Garg

Keyword(s):

Solid Lipid Nanoparticles ◽

Quality By Design ◽

Lipid Nanoparticles ◽

Lymphatic Transport ◽

Quetiapine Fumarate ◽

Solid Lipid ◽

First Pass Metabolism ◽

First Pass ◽

Quality By Design Approach ◽

Pass Metabolism

Background: Quetiapine fumarate, a 2nd generation anti-psychotic drug has oral bioavailability of 9% because of hepatic first pass metabolism. Reports suggest that co-administration of drugs with lipids affects their absorption pathways, enhances lymphatic transport thus bypassing hepatic first-pass metabolism resulting in enhanced bioavailability. Objective: The present work aimed at developing, and characterising potentially lymphatic absorbable Solid Lipid Nanoparticles (SLN) of quetiapine fumarate by Quality by Design approach. Method: Hot emulsification followed by ultrasonication was used as a method of preparation. Precirol ATO5, Phospholipon 90G and Poloxamer 188 were used as a lipid, stabilizer and surfactant respectively. A32 Central Composite design optimised the 2 independent variables, lipid concentration and stabilizer concentration and assessed their effect on percent Entrapment Efficiency (%EE: Y1). The lyophilized SLNs were studied for stability at 5 ±3οC and 25 ± 2οC/60 ± 5% RH for 3 months. Results: The optimised formula derived for SLN had 270mg Precirol ATO5 and 107mg of Phospholipon 90G giving %EE of 76.53%. Mean particle size was 159.8nm with polydispersity index 0.273 and zeta potential -6.6mV. In-vitro drug release followed Korsmeyer-Peppas kinetics (R2=0.917) with release exponent n=0.722 indicating non-Fickian diffusion. Transmission electron microscopy images exhibited particles to be spherical and smooth. Fourier-transform infrared spectroscopy, differential scanning calorimetry and X-ray diffraction studies ascertained drug-excipient compatibility. Stability studies suggested 5οC as appropriate temperature for storage and preserving important characteristics within acceptable limits. Conclusion: Development and optimisation by Quality by Design were justified as it yielded SLN having acceptable characteristics and potential application for intestinal lymphatic transport.

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