Environmentally Responsive Nanoparticles for Delivery as Assessed via Light Scattering and Near-infrared Imaging

Sep 1, 2010 | Contact Author | By: Andrew Harper; Steve Tonge, PhD; Lisa Makein, PhD; Mike Kaszuba, PhD; and Malcolm Connah, PhD, Malvern
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Title: Environmentally Responsive Nanoparticles for Delivery as Assessed via Light Scattering and Near-infrared Imaging
nanoparticlex deliveryx light scatteringx near-infrared chemical imagingx stratum corneum penetrationx
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Keywords: nanoparticle | delivery | light scattering | near-infrared chemical imaging | stratum corneum penetration

Abstract: Lipid-based nanoparticles were developed to respond to environmental stimuli and used as site-directed delivery systems. Through Dynamic Light Scattering (DLS), the self-assembly of these 10–40 nm particles was observed. In addition, the penetration of the particles through the stratum corneum was monitored in vivo using a novel Near-infrared Chemical Imaging (NIR-CI) technique.

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A Harper, S Tonge, L Makein, M Kaszuba and M Connah, Environmentally responsive nanoparticles for delivery as assessed via light scattering and near-infrared imaging, Cosm & Toil 125(9) 52-57 (Sep 2010)

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It has been extensively reported that particles of submicron dimensions can penetrate the stratum corneum (SC); however, this remains a controversial area and was recently refuted in the case of solid nanoparticles, e.g. zinc oxide. In vivo studies by Lademan et al. also demonstrated that particles having dimensions of greater than 40 nm fail to penetrate the intact SC through cellular or paracellular pathways, and only appear to penetrate via a follicular route. Yet other contradictory work warrants the further investigation of particles < 100 nm into the SC; for instance, ex vivo skin studies have shown that rigid metallic nanoparticles of < 10 nm can penetrate the SC. In addition, elastic phospholipid vesicles of approximately 100 nm have been shown in vivo to penetrate the SC, to a greater extent than nonelastic vesicles of similar dimensions.10 This suggests a role for elastic nanostructures with dimensions on the order of 10 nm.

Therefore, based upon the structure of naturally occurring high-density lipoproteins (HDL), nanoparticles of reduced size and controlled dimensions were developeda to topically deliver oil-soluble cosmeceuticals and active agents into the stratum corneum (SC). These particles range from 10 to 40 nm, much smaller than standard carriers such as liposomes (50 to > 1,000 nm).


Lab Practical: Formulating with the Environmentally Responsive Nanoparticles

  • The described nanoparticles, with the chosen active principle, can be formed in the aqueous phase of the cosmetic production process; further temperature rises should not be allowed to exceed 60°C.
  • After formation, the nanoparticle solution is insensitive to pH modification and high speed stir, although homogenization should be avoided.
  • Once formed, the nanoparticles are compatible with most conventional cosmetic ingredients and excipients, although hydroalcoholic bases should be avoided.
  • Ingredients that are lipophillic in nature, such as steroidal compounds, are best adapted for incorporation into and delivery by the nanoparticles. Other examples of particularly well-suited active agents include: vitamins (A, D and E), lipophilic botanical extracts, hydrophobicized peptides and anti-fungals.
  • For optimal dermal penetration of the nanoparticles, the final formulation should be in the form of a gel or solution.

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Figure 1. Schematic of described nanoparticles

Figure 1. Schematic of described nanoparticles

Schematic of nanoparticles composed of a hydrophilic shell and hydrophobic core in which oily active agents can be contained

Figure 2. Controlling particle size by variation of chaperone molecular shape

Figure 2. Controlling particle size by variation of chaperone molecular shape

Controlling particle size by variation of chaperone molecular shape; a high HLB surfactant with a low critical packing parameter and larger head group forms smaller diameter particles (left), while a lower HLB surfactant with a higher critical packing parameter14 and smaller head group forms larger particles (right).

Figure 3. Intensity weighted mean particle diameters

Figure 3. Intensity weighted mean particle diameters

Intensity weighted mean particle diameters obtained as a function of temperature for a polysorbate 20 and phospholipid nanoparticle suspension and polysorbate surfactant solution alone

Figure 4. NIR-IC spectroscopic image of concatenated signal score of marker dye

Figure 4. NIR-IC spectroscopic image of concatenated signal score of marker dye

NIR-IC spectroscopic image of concatenated signal score of marker dye contained on tape strips removed from skin—first removed strip [1] (top left) to the sixteenth [16] removed (bottom right) strip—showing accumulation of dye in the fourteenth [14] strip

Figure 5. NIR-IC spectroscopic image of concatenated averaged signal score of scanned pixel data

Figure 5. NIR-IC spectroscopic image of concatenated averaged signal score of scanned pixel data

NIR-IC spectroscopic image of concatenated averaged signal score of scanned pixel data from tape strips 1–16 showing accumulation of marker dye in the fourteenth (darke red) strip

Footnotes [Harper 125(9)]

a Lipodisq (INCI: Water (aqua) (and) Polysorbate 20 (and) Lecithin (and) preservatives) is a product of Malvern Cosmeceutics, Ltd.

b The Malvern Zetasizer Nano S device used for this study is manufactured by Malvern Instruments Ltd. Malvern, Worcestershire, UK.

c The SyNIRgi system used for this study is manufactured by Malvern Instruments Ltd.

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