lipophilic substances and lipid encapsulation with nanostructured lipid carriers, cyclodextrins and intramolecular hydrogen bonds (IHBs)

[krohm]

I'm looking at ways to increase oral and sublingual absorption of lipophilic substances such as thc, resveratrol, among others, and have come across nanostructured lipid carriers, cyclodextrins and intramolecular hydrogen bonds (IHBs) as potential absorption agents. I've also used and read about lecithin as an absorption agent.

 

From a study I was reading on intramolecular hydrogen bonding (IHBs), 'Intramolecular hydrogen bonding to improve membrane permeability and absorption in beyond rule of five chemical space', Alex et al, 2011, it states:

'Evidence for increased membrane permeability through IHB ring systems is supported by higher Mw cyclic compounds such as cyclosporine A (CsA)19 and other non-natural cyclic peptides.17 CsA is reported to exhibit oral bioavailability of about 30% which is remarkable given its significant deviation from Ro5 space.20 It is now known that CsA exhibits very different conformations depending on the nature of media in which it is contained.19,21 We hypothesise that a conformation of CsA in non-polar media, such as deuterated chloroform or carbon tetrachloride, closely represents a conformation that permeates through the lipid interior of the membrane, as these solvents have a similar dielectric constant to that estimated to exist in the interior of a phospholipid bilayer.17,22'

The paper also states: 'The formation of an IHB can not only potentially increase the permeability of molecules across the intestinal membrane but also across the blood brain barrier.'

 

A paper on cyclodextrins, 'Exploring versatile applications of cyclodextrins an overview, Sharma & Baldi, 2016' states:

The CD permeability through the biological membranes is affected by various factors like its molecular weight, chemical structure and very low octanol/water partition coefficient (log P values) resulting in its inability to cross the biological membranes quickly.'

The article states, 'Whether CD increases or decreases the drug delivery across the biological membrane will depend upon the factors like the physicochemical properties of the drug such as its aqueous solubility, the composition of the drug formulation, i.e. aqueous or non-aqueous and physiological composition of the membrane barrier like the presence of an aqueous diffusion layer (Rasheed et al., 2008).'

'The drug delivery through aqueous diffusion-controlled barriers can be increased by the use of CDs, but it restricts the drug delivery through lipophilic membrane-controlled barriers. Still, there is an exception to it, i.e. hydrophobic CDs (e.g. methylated b-CDs) can easily pass through mucosa and helps to improve the drug delivery through biological membranes, like the nasal mucosa, by decreasing the barrier property of the membranes (Loftsson et al., 2005).'

 

Other absorption and binding agents like lecithin are used in pharmaceuticals and nutraceuticals.

 

Which delivery method should I be considering to increase the absorption of lipophilic substances via mucosal, oral and sublingual delivery using IHBs, CDs, nanostructured or lipid carriers? Or something else?

 

How could I go about trying to find someone to consult professionally on this matter?

 

 

[krohm]

No reply?

Is there anywhere I can go to speak to chemists about something like this?

Are there other forums that I should be looking at?