Research Progress on Application of Borneol as Permeation Enhancer in Functional Cosmetics

Xu Yuanyu,Chen Yuxu,Zhang Jingqing,Zhao Zhimin,Yang Depo,Xu Xinjun

College of Pharmacy,Sun Yat-sen University,China;

Wang Shidong

Guangdong Yuansi South Pharmaceutical Biotechnology Co.,Ltd.,China

Abstract Borneol,as a traditional natural permeation enhancer,has been widely used to promote the transdermal absorption of active ingredients.The mechanism of borneol in promoting permeation by destroying the highly ordered lipid structure of the lipid layer and by destroying the hydrogen-bond network was described.The application of borneol in promoting the transdermal absorption of the active ingredients of traditional Chinese medicine and chemical drugs was introduced.The application of borneol as a natural ingredient added to functional cosmetics was summarized,and its effects on skin-spot treatment,acne skin care,eczema skin care,skin repair and anti-oxidation were introduced.Finally,the possible problems in the application of borneol in cosmetics were put forward,and the application prospect of borneol in the development of cosmetics was given.

Key words borneol;permeation enhancer;cosmetics

Borneol,known as “Bing Pian” and “Long Nao”in traditional Chinese medicine (TCM),is a white or translucent flake-like crystal.It is fragrant,pungent and cool in flavor,with the effects of opening the mind,clearing heat and relieving pain.Currently,d-borneol,l-borneol and synthetic borneol (dl-borneol)are available for various uses,of which the first two belong to natural borneol.l-borneol is extracted from the branches and leaves of Cinnamomum camphora(L.) Presl.d-borneol,also called “Ai Pian”,is obtained from leaves of Blumea balsamifera (L.) DC.Synthetic borneol,which is racemic,is mainly used in clinical practice due to the shortage of natural resources[1].All these types have similar natures,flavors,meridian entry,functions and dosages,so there is no strict differentiation between them in clinical and research applications[2].

Natural permeation enhancers have attracted the attention of researchers because of their low toxicity and minimal side effects.Borneol,classified as a resuscitation-inducing aromatic drug,is one of the widely used volatile oil-based permeation enhancers.As stated in “Ben Cao Yan Yi”,Borneol commonly acts as a “guide drug” or “adjuvant”,combined with other TCMs to enhance their therapeutic effects.In ancient China,there have been various secret recipes for beauty related to borneol,functioning in moisturizing the skin and keeping the cheeks glowing.Recordedin the “Qing Gong Pei Fang Ji Cheng”,“Ou Zi Fang”(Ouzi Formula) is a skin-whitening formula favored by Empress Dowager Cixi,which combined eight traditional Chinese herbs with borneol and cinnabar.

1 Permeation-enhancing mechanism of borneol

Borneol primarily achieves a permeation-enhancing function by disrupting the highly organized lipid structure of the stratum corneum.The influence of borneol on the lipid structure is related to its concentration and temperature.At low borneol concentrations,lipids maintain their bilayer structure as borneol molecules penetrate the lipid bilayer and occupy the hydrophobic space within it.This leads to an increased average area per lipid and disrupts the ordered arrangement of the hydrophobic tails of lipid molecules,making them more flexible and reducing the thickness of the lipid bilayer.At this point,the distance between lipid moleculesincreases,thus enhancing the fluidity and aiding drug permeation.As borneol concentration increases,the lipid structure gradually loosens,leading to the formation of water pores and reverse micelle structures,which further assist drug permeation[3].Researchers discovered that borneol can disrupt the ordered structure of ceramides A and B chains and free fatty acids within the stratum corneum,leading to an increase of the drug diffusion coefficient,and enhancing drug permeation.Borneol has a more significant permeation-enhancing effect on high molecular weight drugs or hydrophilic drugs[4].However,with increasing borneol concentrations,there may be competition for space between borneol and hydrophobic drugs in the hydrophobic region of the bilayer.Therefore,the penetration-enhancing effect of borneol on hydrophobic drugs is limited.At higher borneol concentrations,it may even have an inhibitory effect.Additionally,as the temperature rises,the effect of borneol on the bilayer is enhanced[5].

Ceramides,a key component of the stratum corneum,form a tightly arranged hydrogen-bond network within its lipid structure.Permeation enhancers containing hydrogen bond acceptors or donors can disrupt this network,potentiallyincreasing drug permeation.Borneol,an oxyterpene,can form complexes with drug molecules,improving the distribution of the drug molecules within the stratum corneum and thereby enhancing permeation.The effect of improved distribution is linked to the lipophilicity of drugs[6].Borneol also dilates subcutaneous capillaries,making it easier for drugs to enter the bloodstream and promoting absorption.Additionally,borneol can reduce the expression levels of P-glycoprotein,thus affecting its transport function,thus enhancing drug absorption[7].

2 Application in transdermal drug delivery

Borneol is found widely applied in transdermal drug delivery due to its strong lipophilicity and small molecular weight.Borneol can effectively enhance the transdermal absorption of chemical drugs and activeingredients in TCM.This permeation-enhancing effect reflects a drug-dependent property.In TCM,borneolis known for its dispersing and pungent natures which makes it extensively used in various formulations.Not only do some well-known formulas such as “Bing Peng San” and “Bing Yu San” include borneol,but certain confidential formulas like “Angong Niuhuang Wan,”“Yunnan Baiyao,” and “Liushen Pill” also contain borneol.Modern research indicates that borneol has a promoting effect on the transdermal permeation of some active ingredients of TCM such as emodin,ligustrazine,gastrodin,ferulic acid,epicatechin,icariin and so on[2,8-11].Meanwhile,borneol enhances the transdermal permeation of chemical drugs like aspirin,salicylic acid,fluorouracil,erythromycin,glucosamine,and dexamethasone[12-15].Furthermore,since the penetration-enhancing effect of borneol itself is limited,researchers have turned their attention to novel transdermal drug delivery systems like liposomes and ethosomes that are modified with borneol[16,17].Borneol can compensate for some shortcomings of the novel transdermal drug delivery systems,such as poor transdermal absorption and difficulty in reaching the target site,while these novel carriers can enhance the solubility and stability of borneol,allowing it to better exert its permeation-enhancing effect.

3 Application in cosmetics

With the development of the cosmetic industry,researchers and consumers are fucusing on the concept of “natural,green,and safe”.Combining modern science and technology with TCM theories,cosmetics formulated with natural ingredients as the active components have gained attention in the market.Borneol,a commonly used TCM for beauty and skin care,has been broadly incorporated into multiple beauty recipes since ancient times.In recent years,some popular cosmetic companies have developed skin care products with borneol as the main activeingredient,aiming for effects such as skin whitening and anti-aging.Products like borneol-based acne creams,skin-revitalizing creams,refreshing toners,hydrating facial masks,and microcrystal eye patches have been developed and are now available in the market.Certain personal care products like body splash and shower gel also contain borneol for cooling and refreshing.However,it is worth noting that borneol should be used with caution by pregnant and breastfeeding women,as well as infants and children.Currently,borneol is applied in functional cosmetics for its penetrationenhancing effects in the following aspects.

3.1 Skin spots treatment

Due to its good skin permeability,borneol is often used in the treatment of skin spots to facilitate the permeation of various drugs into the skin for their effects.Borneol has been added in different ancient beauty recipes as an adjuvant ingredient.The “Emperor Face Beauty Cream” for facial yellow spots treatment includes borneol.The “Qufeng Runmian San” for rosacea and blackheads treatment also contains borneol.A face mask formula called “Yu Rong San” containing borneol is effective in treating melasma,age spots,and pregnancyrelated skin discoloration[18].In clinical practice,a TCMbased speckles-removing mask containing Angelica dahurica,Typhoniumh Rhizome and borneol is utilized for treating melasma[19].Besides,borneol is often combined with pearl powder for speckle removal[20].

3.2 Skin care

Acne is a chronic inflammatory skin disease that can have a significant impact on one’s appearance.In clinical formulations aimed at treating skin conditions caused by excessive sebum production such as acne,borneol is often included as it can disrupt the structure of the lipid layer.TCM-based speckles-removing mask contains borneol for enhancing the permeation of other active ingredients[21].For example,“ShenbaiCream”[22]and “Longzhu Ointment”[23]for acne treatment contain borneol.Borneol-containing facial masks and creams also show anti-bacterial effect and can improve skin metabolism,thus promoting the repair of acne-prone skin[24].

Eczema is a skin inflammation disorder caused by a variety of internal and external factors.It often accompanies intense itching,significantly affecting the life quality of patients.Yang et al added borneol to a compound TCM eczema cream and confirmed that the transdermal absorption of the active ingredient,matrine,increased when borneol was added,leading to a significantly improved therapeutic effect on eczema[25].Zhang et al studied the influence of borneol content on the transdermal performance of San Chen microemulsion gel.The results showed that when the concentration of borneol was 3.0%,the microemulsion gel exhibited the best efficacy for eczema treatment[26].

3.3 Skin repair

Due to its influence on the lipid structure of the stratum corneum,borneol can also play a role in skin repair.Pang et al developed a plant-based gel mask with Blumea oil as a natural additive for nighttime skincare and post-sun skin repair[27].Some skin repair creams also incorporate borneol as a functional additive[28].

3.4 Antioxidation effect

Free radicals are metabolic byproducts in the human body that can generally cleared by the oxidative defense systems.However,when free radicals accumulate,aging-related proteins and signaling pathways will be activated,leading to collagen degradation and other reactions that contribute to skin aging[29].Tang et al demonstrated through DPPH radical scavenging tests that natural borneol showed antioxidant capacity with an IC50value of 6.39 mg/mL,though its antioxidant effect is slightly lower than that of vitamin C[30].Research by Tang et al showed that camphor essential oil has a scavenging ability against DPPH and ABTS radicals.Besides,inhaling the essential oil can enhance the antioxidant capacity in mice[31].In summary,Borneol has the potential to eliminate free radicals,thus making it a promising addition to cosmetics.

4 Conclusion and prospect

As a traditional resuscitation-inducing aromatic drug,borneol has been used for thousands of years with abundant research on its permeation-enhancing effects.Various novel drug carriers based on borneol,which combine the advantages of borneol with different drug delivery systems,have significant application potential and research value.To meet the demand of the market,cosmetics derived from natural plant materials have gradually become a trend and a selling point in the industry.Borneol has attractedincreasing attention due to its permeation-enhancing effect and high permeability,especially when usedin conjunction with other beauty and skincareingredients.However,most of these applications are currently just clinical formulations in hospitals.Further research is needed to assess the short-term and long-term safety of cosmetics containing borneol to avoid side effects.Currently,the related products of borneol in cosmetics are mostly masks and creams.In the future,with more studies on the combination of borneol and novel drug delivery systems,borneol may play a broader role in cosmetics.