Delivery Systems. Glycospheres Softspheres 2/27/

Transcription

1 Delivery Systems Glycospheres Softspheres 2/27/2018

2 Why Use Delivery Systems? Target certain areas of the skin Protect active ingredients from degradation when formulated Protect formula from degradation / discoloration due to active ingredients Make formulation easier (ex. insoluble active) Reduce irritations or allergies (limit dermal penetration) Marketing advantages (ex. pack actives in aesthetically pleasing, easily seen particle)

3 Glycospheres Submicron Particles for Protection and Delivery

4 Glycospheres - Structure Stable Porous Core (Quaternarized, Cross-linked Starch) Covalently Bonded Lipid Layer (Fatty Acid Esters) Polar Lipids Layer(s) (Hydrogenated Lecithin) Hydrophilic Lipophilic Hydrophilic Size: 200 nm Suspension in Polar Solvents (Water / Glycols) INCI : Palmitoyl Hydroxypropyl Trimonium / Glycerin Crosspolymer (And) Hydrogenated Lecithin

5 Comparison with Liposomes Liposome Glycosphere ENCAPSULATION: Non Specific Retention Possible leakage if lipid bilayer is weakened ENTRAPMENT: Specific Ionic Bonds between Actives and Cationic Core Actives stay entrapped as long as ionic bond is stable

6 Entrapment : Release Mechanism Low Ionic Strength: No Release High Ionic Strength: Controlled Release Low Water Content / High Ionic Strength conditions prevail in the Stratum Corneum

7 Entrapment & Release Conditions (1) Glycospheres ( ) are too large to go through the filter; entrapped colorant stay in the top compartment Filter Ultrafiltration (0.1µm filter) Filter Non-entrapped or released colorant ( ) goes through the filter and moves to the bottom compartment 1. Non-entrapped colorant goes through the filter 2. Colorant entrapped in Glycospheres stays in the top compartment at low ionic strength (water) 3. When salt is added to the suspension (1M NaCl), colorant is released and moves through the filter to the bottom compartment.

8 Other Entrapment Mechanism Lipophilic molecules are loaded within the lipid layers

9 Physical Characteristics SEM Picture (Freeze Cracking) Stability Over Time (DLS measurement) Time (years) Average Size (nm) S.D. (nm) Freeze-cracked starch core Lecithin layers ½ Average Size and Standard Deviation of Glycospheres in Suspension at Room Temperature Glycospheres are extremely stable (> 3 years at RT); They are also stable at high temperature, low and high ph and in presence of surfactants (data not shown)

10 Skin Adhesion & Penetration Fluorescent Gs (bright white dots) in a stratum corneum layer Glycospheres were tagged with a fluorescent probe, then added to a lotion. The lotion was applied to the skin. After 1 hour, the skin surface was washed. Layers of Stratum Corneum were stripped with an adhesive film Each layer was observed with a fluorescence microscope to determine if Glycospheres stay on the skin after washing and how deep they penetrate. Glycospheres only penetrate into the top layers of the skin (0-15 µm)

11 Protection of Formulas Entrapment and Protection of Procyanidolic Oligomers (PCOs) Polyphenolic compounds. Extracted from plants (ex. grape seed, pine bark). Extremely high free-radical scavenging activity Low stability (discolor over time) Stability of PCO in Emulsion (6 months / 40 C) After 6 months at 40 C non-protected PCOs are polymerized (discoloration & low activity). When entrapped and protected within Glycospheres, they remain stable and active.

12 Protection of Formulas In Vitro Tests NBT & DPPH In Vivo Activity of Formulated PCO Dithranol Test NBT Test (O 2.- ) DPPH Test (OH.) Non-Entrapped PCO Entrapped PCO Non-Entrapped Vit E Entrapped Vit E More active than Vitamin E (variable, depending on test method) Still active when entrapped Stable under UV Light (NBT Test)

13 Stabilization of Ascorbic Acid Entrapped vs. non-entrapped Ascorbic Acid in suspension at high temperature (40 C / 40 days) Gs-Vit.C Glycospheres stabilize Ascorbic Acid even at high temperature Vit.C

14 Stabilization of Papain Papain is an enzyme present in the fruits of Papaya carica, the Papaya tree. It is a proteolytic enzyme which breaks down proteins. In skin care products, it can be used to hydrolyze stratum corneum proteins and promote the elimination of dead skin cells (enzymatic peeling). Other uses include revitalizing hair and restoring shine, tyrosinase inhibition (in skin whitening products), and promotion of fast cell turnover (proteolytic activity). Three-dimentional structure of Papain

15 Proteolytic activity (%) Tyrosinase activity Proteolitic Activity and Tyrosinase Inhibition Proteolytic Activity at 40 C Tyrosinase Inhibition at 40 C Months Days Papain Gs-PPY Papain Gs-PPY The proteolytic activity in solution or entrapped in Glycospheres was tested in vitro (on L-BAPA). Glycosphere-PPY and Papain in an aqueous solution (as control) were kept at 40 C and their activity was measured regularly over a period of one year. The capacity of papain to inhibit melanin synthesis by deactivating tyrosinase was tested in vitro, using tyrosinase and L-DOPA. Glycosphere-PPY and Papain in an aqueous solution (as control) were kept at 40 C and their activity was measured regularly over a period of two months. Papain in solution rapidly loses its activity, but papain protected by the Glycosphere core retains its activity over time at elevated temperatures.

16 Effect of Gs-PPY on Hair Cuticle Untreated hair Hair treated with Papain solution Hair treated with Gs-PPY To evaluate the effect of papain on hair cuticles, tresses were soaked in either water, a papain solution or Gs-PPY. SEM pictures of the cuticle surfaces were then taken. Water and papain solution treatments show rough surface with lifted cuticles, but Gs-PPY treated hair has a smoother surface, which should result in silky and shiny hair.

17 Glycospheres - Summary Chemically stable sub-micron particles Penetration limited to the first layer of the skin Entrapment of both hydrophilic and lipophilic actives Protection of labile molecules from degradation and reaction with formulas Available as suspensions in either water, water and butylene glycol, or water and glycerin Two preservative systems are available: 1. Phenoxyethanol (And) Parabens 2. Pentylene Glycol (And) 1,2-Hexanediol (And) Caprylyl Glycol

18 Examples Trade Names with Preserv. #1 Trade Names with Preserv. #2 Active Ingredient Carrier Cn-HAHWS Sodium Hyaluronate Water Cn-PS2 - Water Cn-UR1000S Urea Water Gs-AHP Acetyl Hexapeptide-8 Water Gs-BC Beta-Carotene Water Gs-GT Green Tea Polyphenols Water Gs-PCOg Grape seed PCOs Water Gs-PPY Papain Water Gs-RES Resveratrol Water Gs-SA2B Salicylic acid Butylene Glycol + Water Gs-VA100C Retinol Butylene Glycol + Water Gs-VACE Ascorbic acid + Tocopherol + Retinol Butylene Glycol + Water Gs-VC40 Ascorbic acid Butylene Glycol + Water Gs-VC2500GDC Ascorbic acid Glycerin + Cyclosiloxane Gs-VC5000 Ascorbic acid Glycerin + Water Gs-VE Tocopherol Water Preservatives: 1- Phenoxyethanol (And) Parabens Available as special order 2- Pentylene Glycol (And) 1,2-Hexanediol (And) Caprylyl Glycol

19 KFL-079A: Anti-Aging Mask

20 KFL-106B-BR: Beauty Booster Serum

21 KFL-107-EU Hydra Mist

22 Softspheres Visual Impact & Delivery

23 Structure Capsules (1) Inner (liquid) material (+ active) Solid wall (+ pigments) Wall has to be solid to avoid inner material(s) from leaking out of the capsule Empty capsules are still visible after breaking on the skin

24 Structure Capsules (2)

25 Structure - Homogeneous Gel Beads (1) No walls : same material inside & outside Gel is weak enough to break and disappear when beads are rubbed onto the skin

26 Structure - Homogeneous Gel Beads (2)

27 Entrapment in Gel Beads (1) Gel forms a matrix There is no wall between outside and inside compartments when the bead is in water (solvent) Water (solvent) can flow in/out of the bead (although at a lower diffusion rate)

28 Entrapment in Gel Beads (2) For the bead to be soft enough, the matrix has to be large Small molecules will diffuse out of the matrix (equilibrium) Large molecules (polymers) will not diffuse through the gel matrix

29 Entrapment in Softspheres (1) Cationic polymer is added to the composition (cannot move) Anionic molecules form ionic bonds with the polymer Anionic molecules cannot diffuse out of the beads

30 Entrapment in Softspheres (2) + Softspheres can entrap within the gel matrix > Ionic small molecules + > Lipophilic products (different polymer) + > Macromolecules > Pigments +

31 Size Size Range: mm 3 «Standard» Sizes: > a = mm > b = mm > m = mm Stable ph 2-10, in surfactants, at temperatures up to 60 C* * May vary with actual composition

32 Composition Agar-Agar Restraining Polymer: Polyquaternium-11 Colorants/Pigments Active Ingredients/Oils/Vitamins/Fragrances/... Preservative systems: 1. Propylene Glycol, Imidazolidinyl Urea, Phenoxyethanol, Parabens 2. Propylene Glycol, Pentylene Glycol, Caprylyl Glycol, 1,2-Hexanediol

33 Applications Examples of active ingredients successfully entrapped in Softspheres Anionic: colorants, hyaluronic acid Lipophilic: tocopherol, vitamin A, natural oils, ceramides Macromolecules: enzymes Pigments: iron, titanium & zinc oxides Miscellaneous: emulsions, fragrances Recommended use levels range from 2.5 to 10% depending on the Softspheres diameter.

34 Softspheres - Summary Large Colored Beads Chemically Stable (ph, Temperature, Surfactants) Decoration of Many Different Types of Formulations Release Active Ingredients by Breaking under Pressure without Leaving Residues on the Skin

35 Examples Trade Names with Preserv. #1 Trade Names with Preserv. #2 Active Ingredient Color SpS-5coral56 Tocopheryl acetate Pearlescent Tan SpS-BkFeO41 - Black Sp-AOPL41 Sweet Almond oil + Tocopheryl ac. Pearlescent Pink Sp-BkFEB41 - Metallic Grey Sp-JbOTiO41 Jojoba Oil White Sp-SfOVEaUMDC41 Sunflower Seed Oil + Tocopheryl ac. Pearlescent Blue Sp-UM41 - Deep Blue Sp-VApGP41 Retinyl Palmitate Gold Sp-VCTiOGH Magnesium Ascorbyl Palmitate Light Green Sp-VCYOTR56 Tocopheryl ac. + Mg Ascorbyl Palmitate Orange Sp-VEaVAGrP41 Tocopheryl Ac. + Aloe Barbadensis Leaf Juice Pearlescent Green Sp-VEaDC56 Tocopheryl Acetate Pearlescent White Sp-VEaTR41 Tocopheryl Acetate Red All products are available in 3 sizes (suffixes a = mm - b = mm - m = mm) Preservatives: 1- Propylene Glycol, Imidazolidinyl Urea, Phenoxyethanol, Parabens 2- Propylene Glycol, Pentylene Glycol, Caprylyl Glycol, 1,2-Hexanediol Available as special order

36 KCL-019-EU Grapefruit Shower Gel

37 KCL-004B: Vitamin Rich Body Wash with Softspheres

38 KFL-135C Revitalizing Clear Serum with Softspheres