NanoActive™ Azelaic Acid 50%

ENGLISH VERSIONComplete English Article

PURIPHARM CO., LTD. · TECHNICAL PRESENTATION · COSMETIC ACTIVE INGREDIENT

NANOACTIVE™ SERIES · NANO-ENCAPSULATED ACTIVES

NanoActive™Azelaic Acid 50%

Nano-encapsulated Azelaic Acid 50%

Multi-pathway skin clarification · Pigment management · Follicular clarification

Abstract: 50% high-payload azelaic acid combined with next-generation nanoliposome delivery. Four published evidence pathways—keratinization regulation, microbiome clarification, inflammation modulation, and pigment management—address the classic formulation paradox of an effective but difficult-to-formulate molecule.

PART II · ENGLISH VERSION

POSITIONING · PRODUCT POSITIONING

Re-engineering how azelaic acid is delivered

50% high-payload azelaic acid × next-generation nano delivery

Powerful multi-pathway biology

↓

A difficult-to-formulate molecule

↓

PURISOME® nanoliposome delivery

↓

Modern azelaic acid formulation

Azelaic acid has long-established value in blemish-prone skin, pigmentation, and follicular biology. Its main limitation is formulation and delivery rather than efficacy. NanoActive™ Azelaic Acid 50% addresses this classic paradox through a 50% active payload and PURISOME® nanoliposome delivery.

ONE MOLECULE · MULTIPLE PATHWAYS

The multidimensional biology of azelaic acid

Azelaic acid is more than an anti-acne ingredient. It is one of the few multifunctional actives that simultaneously addresses keratinization, the microbiome, inflammation, and pigmentation pathways.

Keratinization regulation

Regulates terminal differentiation of keratinocytes in the follicular infundibulum and helps reduce follicular keratin buildup at its source.

Microbiome clarification + inflammation modulation

Interferes with intracellular bacterial protein synthesis, reduces neutrophil ROS release, and modulates inflammatory signaling.

Pigment management

Competitively inhibits tyrosinase to support the management of post-acne marks, visible hyperpigmentation, and uneven tone.

Follicular and scalp microenvironment

Published evidence of follicular accumulation extends its potential use to scalp and follicular care.

Blemish-prone skin · Abnormal keratinization · Microbiome · Visible inflammation · Post-acne marks · Uneven tone · Oxidative stress · Follicular and scalp care: multiple pathways addressed by one molecule.

THE FORMULATION PARADOX

Effective, yet difficult to formulate

≈ 0.24%

Intrinsic water solubility of azelaic acid at 20°C · reported in the literature

15–20%

Use levels in established topical efficacy research · historical literature and pharmaceutical products

How can a high-dose, poorly soluble molecule be incorporated into an elegant modern formulation?

Note: 15–20% refers to use levels in historical literature and pharmaceutical products. It illustrates the formulation challenge and does not represent a recommended cosmetic use level for NanoActive™ Azelaic Acid 50%.

MECHANISM I · KERATINIZATION REGULATION

Keratinization regulation: reducing follicular keratin buildup at the source

Abnormal keratinocyte differentiation

↓

Follicular hyperkeratinization

↓

Microcomedone formation

↓

Comedones and clogged pores

↓

Inflammatory lesions

Published evidence shows that azelaic acid has antikeratinizing activity and helps restore disrupted terminal differentiation of keratinocytes in the follicular infundibulum.

Reduces follicular hyperkeratosis
Decreases the number and volume of keratohyalin granules
Improves abnormal follicular keratinization and restores terminal keratinocyte differentiation

Cosmetic value positioning: helps reduce follicular keratin buildup at its source.

Pathological sequence in acne-prone follicles: abnormal keratinization is the starting point. Normal Follicle vs Hyperkeratinized Follicle.

PUBLISHED EVIDENCE · HISTOLOGIC EVIDENCE OF KERATINIZATION NORMALIZATION

Marked reduction and normalization of hyperkeratosis after 8–12 weeks

8–12 weeks

20% azelaic acid cream, applied twice dailyMarked reduction or normalization of intrafollicular and interfollicular hyperkeratosis

Marked reduction in hyperkeratosis

Histologic observations showed marked improvement or normalization of both intrafollicular and interfollicular hyperkeratosis.

Fewer and smaller keratohyalin granules

The number and size of keratohyalin granules decreased, indicating normalization of the keratinization process.

Normalization of terminal keratinocyte differentiation

Disrupted terminal differentiation was corrected, restoring a healthier follicular keratinization pattern.

Gollnick H. Azelaic acid — pharmacology, toxicology and mechanisms of action on keratinization in vitro and in vivo. J Dermatol Treat. 1993.Published evidence on conventional azelaic acid formulations; not a finished-product clinical trial of NanoActive™ Azelaic Acid 50%.

MECHANISM II · FOLLICULAR MICROBIOME

Follicular microbiome: antimicrobial action from within the cell

Azelaic acid

↓

Transport into the bacterial cell

↓

Interference with intracellular protein synthesis

↓

Reduced microbial growth and proliferation

This is more specific than a general claim of “killing acne bacteria.” Published mechanistic research indicates that azelaic acid enters bacterial cells via transport mechanisms and interferes with intracellular protein synthesis, thereby reducing microbial growth and proliferation.

Cutibacterium acnes

Formerly Propionibacterium acnes; the historical name is retained when citing original publications.

Staphylococcus epidermidis

A resident skin bacterium examined in microbiome-related research.

PUBLISHED EVIDENCE · ANTIMICROBIAL ACTION

At least 96% reduction in skin-surface and follicular-associated bacteria after 8 weeks

≥96%

Reduction in bacteria sampled from the skin surface and follicles

20%

Azelaic acid cream

8 weeks

Topical treatment period

Surface + follicle

Two sampling levels

After 8 weeks of topical treatment with 20% azelaic acid cream, counts of propionibacteria and staphylococci on the skin surface and within follicles fell by at least 96%, demonstrating microbiome clarification that reaches into the follicle.

Holland KT, Bojar RA. Antimicrobial effects of azelaic acid. J Dermatol Treat. 1993.Published evidence using a conventional 20% azelaic acid cream; not a finished-product clinical trial of NanoActive™ Azelaic Acid 50%.

MECHANISM III · ROS & INFLAMMATION

Reducing oxidative stress and modulating inflammatory signals

Azelaic acid

↓

Reduced neutrophil ROS release

↓

Lower oxidative inflammatory burden

Pathway examined in published research: CD36 → NADPH oxidase → ROS → MAPK → NF-κB

The literature reports that azelaic acid can reduce reactive oxygen species generation and downregulate oxidative inflammatory cascades. Related studies also involve innate immune signaling nodes such as TLR2, KLK5, and LL-37/cathelicidin, although the strength of evidence varies by target.

Soothes blemish-prone skin

Cosmetic value

Supports improvement in the appearance of redness

Cosmetic value

Improves the inflammatory environment around clogged follicles

Cosmetic value

Supports a healthier-looking skin texture

Cosmetic value

CLINICAL EVIDENCE · INFLAMMATORY LESIONS

Greater reduction in inflammatory lesion counts with 15% azelaic acid gel

251 adult patients
Moderate-to-severe papulopustular rosacea
15-week controlled clinical study
15% azelaic acid gel vs active comparator gel; the azelaic acid group had a greater mean reduction in inflammatory lesion count

This evidence supports the anti-inflammatory skin biology of azelaic acid. The comparator is described generically and no commercial brand is identified.

Elewski BE, et al. A comparison of 15% azelaic acid gel and 0.75% metronidazole gel in the topical treatment of papulopustular rosacea. Arch Dermatol. 2003;139:1444–1450.

MECHANISM IV · PIGMENT CONTROL

Pigment management through competitive tyrosinase inhibition

L-Tyrosine

↓

Tyrosinasecompetitively inhibited by azelaic acid

↓

L-DOPA

↓

Dopaquinone

↓

Melanin

Azelaic acid has been reported to competitively inhibit tyrosinase and to have specific biological relevance in hyperactive melanocyte systems. Together with reduced ROS, modulation of melanogenesis, and improvement of the post-inflammatory environment, this forms a more complete pigment-management pathway. Azelaic acid is not a bleaching agent; it is a multi-pathway pigment-management active.

Post-acne marks
Uneven tone
Visible hyperpigmentation
Management of dullness and skin clarity

CLINICAL EVIDENCE · HYPERPIGMENTATION

20% azelaic acid: an established clinical foundation for pigment management

Randomized, double-blind, controlled clinical study
329 female participants
24 weeks · 20% azelaic acid vs 4% hydroquinone
Median reduction in lesion area: approximately 71% vs approximately 78%
Good/excellent overall improvement: 64.8% vs 72.5%
No statistically significant difference between groups in overall improvement

Clinical research in melasma and other hyperpigmentation concerns shows that azelaic acid has an efficacy foundation comparable with that of a classic reference ingredient.

Gupta AK, et al. The treatment of melasma: A review of clinical trials. J Am Acad Dermatol. 2006;55:1048–1065.

POST-ACNE MARKS · FROM BLEMISH TO MARK

Pigmentation may persist after the blemish resolves

Follicular blockage

↓

Inflammation

↓

ROS / inflammatory mediators

↓

Melanocyte activation

↓

Post-inflammatory hyperpigmentationPIH / post-acne marks

Five stages addressed by azelaic acid: keratinization, the inflammatory environment, microbiome balance, tyrosinase, and oxidative stress.

From blemish to mark: one active addresses a more complete biological pathway.

FOLLICULAR DELIVERY MATTERS · EVIDENCE OF FOLLICULAR ACCUMULATION

The follicle is where azelaic acid needs to reach

Single topical application of 20% azelaic acid cream
9 healthy adults · forehead and back
Follicular casts collected over 5 hours
Measurable accumulation of azelaic acid in the pilosebaceous unit

36–251

mmol/L · estimated peak concentration in back follicles

2–112

mmol/L · estimated peak concentration in forehead follicles

Follicular concentrations reached or exceeded the concentrations required to inhibit C. acnes and S. epidermidis in vitro. This provides a scientific foundation for the PURISOME® follicular-delivery concept.

Bojar RA, et al. Follicular concentrations of azelaic acid after a single topical application. Br J Dermatol. 1993;129:399–402.Published data on a conventional azelaic acid formulation; not a NanoActive™ Azelaic Acid 50% product study.

WHY NANO DELIVERY MATTERS

Azelaic acid needs better delivery, not proof of efficacy

Formulation realities of conventional azelaic acid	NanoActive™ delivery rationale
Extremely low intrinsic water solubility (≈0.24% at 20°C)	NanoActive™ Azelaic Acid 50%
Historical products rely on high effective use levels	PURISOME® liposomal delivery · high active payload
Risk of crystallization, recrystallization, and particles	Improved formulation compatibility · lower free-crystal burden
Risk of a gritty skin feel and high solids loading	Controlled skin and follicular delivery
Difficult to incorporate into low-viscosity, transparent modern dosage forms
Limited suitability for serums and scalp formats

Delivery efficiency, not simply the concentration added.

SCIENTIFIC PRECEDENT · PHOSPHOLIPID VESICLE DELIVERY

Vesicular delivery of azelaic acid: scientific exploration since 2004

As early as 2004, azelaic acid was systematically investigated in phospholipid-based vesicular systems, including liposomes and ethosomes. Vesicle morphology, particle-size distribution, and in vitro release were fully characterized.

Characterization of phospholipid vesicle morphology and size distribution
Franz-cell in vitro release curves
Systematic comparison of release from liposomes and ethosomes

Phospholipid-vesicle delivery is an established scientific strategy for improving topical azelaic acid formulation and release behavior.

Esposito E, et al. Ethosomes and liposomes as topical vehicles for azelaic acid: A preformulation study. J Cosmet Sci. 2004;55:253–264.

PUBLISHED PROOF OF CONCEPT · LIPOSOMAL AZELAIC ACID

10% liposomal azelaic acid produced greater stratum corneum deposition than a conventional 20% formulation

Approximate liposome diameter: 211 nm
PDI ≈ 0.22–0.24, indicating a uniform distribution
With half the active concentration, stratum corneum deposition increased 2.3–3.6-fold

Delivery efficiency, not simply the concentration added.

Burchacka E, et al. Biomed Pharmacother. 2016;83:771–775. DOI: 10.1016/j.biopha.2016.07.014An independently published proof-of-concept study of liposomal azelaic acid; not PURISOME® technology data.

DELIVERY TECHNOLOGY

PURISOME® FlexVes™

A delivery system redesigned for high-payload azelaic acid

PURISOME® is PuriPharm’s proprietary nanoliposome delivery platform. Nanoscale phospholipid-bilayer vesicles carry a 50% azelaic acid payload from an aqueous environment, through the stratum corneum and follicular openings, to support local accumulation and controlled release.

Improved formulation compatibility

FORMULATION

Optimized skin and follicular delivery

DELIVERY

Sustained release

CONTROL

Improved user experience with a high active load

COMFORT

PRODUCT PROFILE

NanoActive™ Azelaic Acid 50%

Nano-encapsulated Azelaic Acid 50% · Powered by PURISOME® FlexVes™ Liposome Technology

Product name	NanoActive™ Azelaic Acid 50%
INCI	Azelaic Acid
Active content	50% azelaic acid (raw-material active-payload specification)
Delivery technology	PURISOME® FlexVes™ Liposome Technology
Active molecule	Azelaic acid
Chemical class	Saturated C9 dicarboxylic acid
Molecular formula	C9H16O4
Molecular weight	188.22
Structural formula	HOOC–(CH2)7–COOH

Azelaic acid is a naturally occurring saturated nine-carbon dicarboxylic acid. The 50% figure is the raw material’s active-content specification, not the use concentration in a finished product. Particle size, pH, recommended use level, and other technical parameters should follow the latest PuriPharm TDS.

HIGH ACTIVE PAYLOAD

50% azelaic acid active payload

50%

AZELAIC ACID PAYLOAD

50% high active payload

↓

PURISOME® nano delivery

↓

Greater formulation freedom

50% is the active-content specification of the raw material, not the use concentration in a finished formulation.

A high-payload raw material allows formulators to deliver a meaningful azelaic acid level without introducing excessive carrier material into the finished product. This preserves valuable formulation space for refining skin feel, stability, and dosage form, leaving genuine freedom for serums, gels, emulsions, and scalp formats.

DELIVERY MECHANISM

Controlled release from the aqueous phase into the follicle

Aqueous environment

↓

Nanolipid vesicles

↓

Stratum corneum

↓

Follicular opening

↓

Local controlled release

Nanoscale phospholipid vesicles carry azelaic acid along the skin surface and follicular pathways, supporting local accumulation and sustained release in the target area. In this way, the delivery destination becomes part of formulation design.

BLEMISH-PRONE SKIN · MULTI-PATHWAY CARE

Azelaic acid addresses three of the four acne pathways

Pathway	Role	Description
Follicular hyperkeratinization	Core action	Regulates keratinization and addresses the source of follicular blockage
Microbial colonization	Core action	Interferes with intracellular bacterial protein synthesis and clarifies the follicular microbiome
Inflammation / ROS	Core action	Reduces oxidative stress and modulates inflammatory signaling
Sebum–follicle environment	Associated environment	Indirectly relates to this pathway by improving the follicular microenvironment

Scientific rigor note: current literature does not support a claim that azelaic acid directly suppresses sebum secretion, so no such claim is made here. Its value lies in acting simultaneously on three core pathways: keratinization, the microbiome, and inflammatory oxidative stress.

Multi-pathway management for blemish-prone skin: a complete path from keratinization and the microbiome to inflammation and pigmentation.

COMBINATION INSPIRATION · COMBINATION RESEARCH

Azelaic acid × salicylic acid: clinical exploration of a multi-pathway combination

Study design · randomized controlled trial	Published results
34 patients with acne · split-face design	Inflammatory and non-inflammatory acne lesions improved significantly on both sides
4 treatments · 2-week intervals	The SA + AA side produced higher patient satisfaction and less discomfort
20% salicylic acid + 20% azelaic acid
Comparator side: 25% trichloroacetic acid (TCA) chemical peel

Azelaic acid can be combined with other keratinization-regulating actives to build multi-pathway solutions for blemish-prone skin.

This was a clinical chemical-peel protocol. It is presented as scientific inspiration for combination concepts and does not constitute a cosmetic formulation recommendation or concentration guideline.

Abdel Hay R, et al. Clinical and dermoscopic evaluation of combined salicylic acid 20% and azelaic acid 20% versus trichloroacetic acid 25% chemical peel in acne: an RCT. J Dermatolog Treat. 2019;30(6):572–577. DOI: 10.1080/09546634.2018.1484876

SCALP CARE

From skin follicles to scalp follicles

The same follicular biology also applies to the scalp. Scalp care involves more than oil control.

Six microenvironmental concerns in scalp follicles: keratin buildup, follicular blockage, the inflammatory environment, microbiome balance, oxidative stress, and the sebum environment.

Care for oily scalp · clarifying scalp formulas
Follicular cleansing · acne-prone scalp
Scalp microbiome management
Scalp soothing and renewal

HAIR-FOLLICLE BIOLOGY

5α-reductase: an exploratory mechanism for scalp applications

Testosterone

↓

5α-Reductasepresent in human hair follicles

↓

DHT

Published biochemical research examined the inhibitory effect of azelaic acid—particularly when combined with zinc—on 5α-reductase activity in human skin. This provides mechanistic scientific support for exploring scalp applications.

Scientifically rigorous product-development language:

Supports management of the follicular microenvironment
Research on 5α-reductase-related mechanisms provides a new scientific direction for scalp applications
Provides a mechanistic product-development rationale for oily-scalp and androgen-related follicular care

Stamatiadis D, et al. Inhibition of 5α-reductase activity in human skin by zinc and azelaic acid. Br J Dermatol. 1988;119:627–632.

APPLICATION MAP

One active for the face, body, and scalp

FACE

Anti-blemish oil-control serumPore-care serumPost-acne mark repair serumBrightening serumUneven-tone careRedness-care formulaMoisturizer for oily skinClarifying cleanser

BODY

Back-acne careChest-acne careBody hyperpigmentation serumFollicular roughness care

SCALP

Clarifying scalp serumOily-scalp serumFollicular-care serumScalp keratinization careSoothing scalp productsClarifying shampooHair-root serum

All application directions are positioned for cosmetic use. Compatibility with specific dosage forms should follow the latest PuriPharm TDS and formulation support.

COMPARISON · FORMULATION VALUE

Conventional azelaic acid powder vs NanoActive™ Azelaic Acid 50%

Dimension	Conventional azelaic acid powder	NanoActive™ Azelaic Acid 50%
Aqueous-phase compatibility	Extremely low intrinsic water solubility (≈0.24% at 20°C)	Pre-engineered nanodispersion system
Dispersion difficulty	Requires solubilization or suspension strategies	Uniform dispersion and easy incorporation
Solids loading	High use levels create a high solids load	50% high payload reduces formulation burden
Crystallization management	Free crystalline active; recrystallization must be controlled	Carrier-associated active delivery
Skin feel	Risk of grittiness	Smooth sensory profile designed for modern formats
Delivery strategy	Primarily passive diffusion	PURISOME® nanoliposome delivery
Follicular delivery	Limited potential	Delivery designed for the follicular pathway
Release behavior	Sustained release is difficult to achieve	Carrier-mediated sustained release
Formulation flexibility	Mainly high-viscosity suspension formats	Serums / gels / emulsions / scalp formats
Scalp suitability	Difficult	Good

KEY VALUE PROPOSITION

Making high-concentration azelaic acid more suitable for next-generation formulations

Multi-pathway azelaic acid biology

MULTI-ACTION

50% high payload

HIGH PAYLOAD

PURISOME® nano delivery

PRECISION DELIVERY

Greater freedom for modern formulations

FORMULATION FREEDOM

From facial blemish-prone skin to scalp-follicle care

SKIN + SCALP

NanoActive™ Azelaic Acid 50%

NanoActive™ Azelaic Acid 50%Powered by PURISOME® FlexVes™ Liposome TechnologyPuriPharm Co., Ltd. · www.puriactives.com · service@puripharm.com