|
| ORIGINAL ARTICLE |
|
|
|
| Year : 2007 | Volume
: 73
| Issue : 1 | Page : 22-25 |
The efficacy of 5% topical tea tree oil gel in mild to moderate acne vulgaris: A randomized, double-blind placebo-controlled study
Shahla Enshaieh1, Abolfazl Jooya1, Amir Hossein Siadat2, Fariba Iraji1
1 Department of Dermatology, Skin Diseases and Leishmaniasis Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
2 Consultant Dermatologist, Skin Diseases and Leishmaniasis Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
Correspondence Address:
Abolfazl Jooya
Department of Dermatology, Al-Zahra Hospital, P.O. Box: 892, Isfahan
Iran
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0378-6323.30646
Background: Finding an effective treatment for acne that is well tolerated by the patients is a challenge. One study has suggested the efficacy of tea tree oil in treatment of the acne vulgaris. Aim: To determine the efficacy of tea tree oil in mild to moderate acne vulgaris. Methods: This was a randomized double-blind clinical trial performed in 60 patients with mild to moderate acne vulgaris. They were randomly divided into two groups and were treated with tea tree oil gel (n=30) or placebo (n=30). They were followed every 15 days for a period of 45 days. Response to treatment was evaluated by the total acne lesions counting (TLC) and acne severity index (ASI). The data was analyzed statistically using t-test and by SPSS program. Results: There were no significant differences regarding demographic characteristics between the two groups. There was a significant difference between tea tree oil gel and placebo in the improvement of the TLC and also regarding improvement of the ASI. In terms of TLC and ASI, tea tree oil gel was 3.55 times and 5.75 times more effective than placebo respectively. Side-effects with both groups were relatively similar and tolerable. Conclusion: Topical 5% tea tree oil is an effective treatment for mild to moderate acne vulgaris.
Keywords: Acne vulgaris, Tea tree oil gel, Topical treatment
How to cite this article:
Enshaieh S, Jooya A, Siadat AH, Iraji F. The efficacy of 5% topical tea tree oil gel in mild to moderate acne vulgaris: A randomized, double-blind placebo-controlled study. Indian J Dermatol Venereol Leprol 2007;73:22-5 |
How to cite this URL:
Enshaieh S, Jooya A, Siadat AH, Iraji F. The efficacy of 5% topical tea tree oil gel in mild to moderate acne vulgaris: A randomized, double-blind placebo-controlled study. Indian J Dermatol Venereol Leprol [serial online] 2007 [cited 2021 Jan 21];73:22-5. Available from: https://www.ijdvl.com/text.asp?2007/73/1/22/30646 |
| Introduction | |  |
Acne vulgaris remains one of the commonest diseases to afflict humanity. The analysis of the 1996 census data in the United States of America indicated that the prevalence of acne in the age group 12-24 was 85%.[1] Even in its mild form, acne can have lingering impacts on mental health (e.g., anxiety and depression), social interactions, self-confidence, self-esteem and employment opportunities.[2] Antibiotics which suppress Propionibacterium acnes are the standard treatment for acne, but are becoming less effective probably because of the emergence of antibiotic-resistant strains.[3],[4],[5],[6] Search for an effective treatment that is well tolerated by patients is a challenge.
Tea tree oil has broad-spectrum antimicrobial[7] and anti-inflammatory[8],[9] activity in vitro .These properties have formed the basis of its use in the treatment of a range of superficial dermatoses such as cuts, insect bites, boils and dermatophytosis.[7],[10] There are study reports suggesting the use of 5% tea tree oil for the treatment of acne vulgaris and showing the efficacy of tea tree oil gel against Propionibacterium acnes.[11] These basic facts prompted us to perform a double-blind placebo-controlled study to determine the efficacy of tea tree oil in the treatment of mild to moderate acne vulgaris.
| Methods | | |
This double-blind clinical trial was performed between December 2004 and September 2005 at our out-patient clinics. A total of 60 patients (age range-15 to 25 years) with mild to moderate facial acne vulgaris (defined as the maximum number of comedones as well as papules and pustules less than 20 and 50 respectively and the absence of any nodules, cysts or sinus tracts)[12] were selected randomly. Ethical Committee clearance was taken before performing this study. Informed consent was also taken from all patients.
We performed this study with 30 patients in each group. Patients were randomized to two groups using random allocation software. Patients in Group A were treated with 5% tea tree oil gel and those in Group B, with placebo (vehicle gel alone). The vehicle gel was composed of the carbomer that had no antiacne activities per se . Tea tree oil and placebo gels were in the same color, texture, package size but with different labels. Both the active drug and the placebo were provided by Cinere Company, Iran. Every patient was interviewed separately so that they were not able to compare their drugs with each other. The patients were instructed to apply the drug or placebo twice daily over the affected area for 20 min and then to wash it off with tap water. The treatment was continued for 45 days. Both investigators and the patients were blinded to the type of treatment.
The patients were seen at every 15-day period to evaluate the lesions and any side-effects. To determine the efficacy of treatment on acne severity we used both total lesion count (TLC) and the acne severity index (ASI).
The ASI[11] was calculated as:
ASI = Papules + (2×pustules) + (comedones/4)
The TLC count was calculated as:
TLC = Papules + pustules + comedones + nodules
The primary outcome measure was defined as the change in mean TLC and ASI scores at the end of treatment compared to baseline in both the study and control groups. Secondary outcome measures included a change in the mean numbers of comedones, papules and pustules.
A second investigator blinded to the type of treatment was responsible for counting the lesions before and after the treatment. In the first visit, the total number of lesions was considered to be 100% and any decrease in the number of lesions was calculated accordingly and regarded as the percentage of improvement. The mean of these percentages of improvement was calculated in each group of patients and used for statistical analysis. At the end of the study, the data were analyzed by the third investigator using SPSS (release 13) program (student's t test) and then the labels were revealed.
| Results | | |
Demographic results
The demographic characteristics of the patients are shown in [Table - 1]. There were no significant differences regarding these characteristics between the two groups ( P value>0.05), confirming the success of randomization. All the patients completed the study.
Efficacy on TLC
The mean TLC in the 5% tea tree oil gel group reduced from 21.16 before treatment to 11.33 after six weeks of treatment, a reduction of 43.64%. This difference was statistically significant ( P value = 0.035, 95% confidence interval (CI) of the difference = 7.05-12.6). The mean TLC in the placebo group dropped from 19.53 before treatment to 17.23 after treatment, i.e., by 12.03%. This difference was not statistically significant ( P value = 0.09, 95% CI of the difference = 1.16-3.43). There was a significant difference between 5% tea tree oil gel and placebo regarding improvement of the TLC ( P value = 0.000, CI of the difference = 21.24-41.98) [Figure - 1]. In terms of the TLC, 5% tea tree oil gel was 3.55 times more effective than placebo.
Efficacy on ASI
The mean ASI in the 5% tea tree oil gel group was 14.18 before treatment and 7.64 after treatment, a reduction of 40.49%. This difference was statistically significant ( P value= 0.000, CI of the difference = 4.51-8.58). In the placebo group, there was 7.04% reduction of the ASI, from a mean ASI of 12.35 before treatment to 11.56 after treatment. This difference was not statistically significant ( P value= 0.051, CI of the difference = -5.2-1.5). There was significant difference between 5% tea tree oil gel and placebo regarding improvement of the ASI [Figure - 1] ( P value = 0.000 CI of the difference = 18.64-48.24). In context of ASI, 5% tea-tree oil gel was 5.75 times more effective than placebo.
Efficacy on comedones number (CN)
The mean of CN in the 5% tea tree oil gel group was 12.23 before treatment and 6.46 after treatment; the CN reduced by 40.24%. This difference was statistically significant ( P value= 0.000, CI of the difference=3.59-7.94). The efficacy of placebo was 12.13% in reduction of CN (from 12.86 before treatment to 10.80 after treatment). This difference was statistically significant ( P value= 0.001 CI of the difference=0.95-3.1). There was a significant difference between 5% tea tree oil gel and placebo regarding improvement of the CN ( P value= 0.000 CI of the difference = 14.33-41.94) [Figure - 2].
Efficacy on papules number (PPN)
The 5% tea tree oil gel reduced PPN as much as 46.06% during six weeks of treatment .The mean of PPN in this group was 6.60 before treatment and 3.56 after treatment. This difference was statistically significant ( P value = 0.004 CI of the difference = 1.85-4.21).The reduction of PPN in the placebo group was calculated to be 9.70%.The mean of PPN in this group was 4.43 before treatment and 4.00 after treatment. This difference was not statistically significant ( P value= 0.056, CI of the difference= -1.2-0.87). There was significant difference between these two groups regarding improvement of the papules number ( P value=0.022; CI of the difference=3.91-49.33) [Figure - 2].
Efficacy on pustules number (PUN)
The 5% tea tree oil gel reduced PUN by as much as 47.45% during six weeks of treatment. The mean of PUN in this group was 2.30 before treatment and 1.23 after treatment. This difference was statistically significant ( P value= 0.001, CI of the difference=0.47-1.65). In the placebo group, there was worsening of the pustular lesions of acne. A reduction of 2.37% in pustules number was noted in the placebo group. The mean of PUN in this group was 2.30 before treatment and 2.36 after treatment. This difference was not statistically significant ( P value= 0.45, CI of the difference= -0.46-0.2). There was a significant difference between these two groups regarding improvement of the pustules number ( P value=0.001, CI of the difference=21.42-78.21) [Figure - 2].
Side-effects of treatment
In the 5% tea tree oil-treated group, three out of 30 patients (10%) complained of minimal pruritus. One patient (3.33%) reported a little burning sensation on application of the drug and another (3.33%) had minimal scaling. In the placebo group, two patients (6.66%) complained of minimal pruritus and two patients (6.66%) reported a little burning sensation on application of the drug.
| Discussion | | |
The essential oil of Melaleuca alternifolia , also known as tea tree oil or Melaleuca oil, has been used medicinally in Australia for more than 80 years.[7] The tree itself has been used therapeutically for even longer, being one of the plants used in traditional medicine by the Bundjalung aborigines of northern New South Wales.[7] Tea tree oil (TTO) is well characterized and contains approximately 100 terpenes and their related alcohols.[13] The physical and chemical properties of commercial TTO are regulated by an international standard.[14]
TTO (batch 971) was kindly provided by Cinere Company, Tehran, Iran. The levels of the components were determined by gas chromatographic analysis according to the international standard.[14] Tea tree oil has broad-spectrum antimicrobial[7] and anti-inflammatory[8],[9],[15],[16] activity in vitro . These properties have formed the basis of its use in the treatment of a range of superficial dermatoses such as cuts, insect bites, boils, acne and dermatophytic infections.[7],[10] Furthermore, data from clinical studies indicate that superficial infections or conditions caused by bacteria,[10] fungi[17] and viruses respond clinically to treatment with tea tree oil.
In a single-blind, randomized clinical trial performed for the evaluation of tea tree oil in acne vulgaris, the efficacy and skin tolerance of 5% tea tree oil gel in the treatment of mild to moderate acne was compared with 5% benzoyl peroxide lotion in 124 patients. The results showed that both 5% tea tree oil and 5% benzoyl peroxide had a significant effect in ameliorating acne by reducing the number of inflammed and noninflammed lesions (open and closed comedones), although the onset of action in case of tea tree oil was slower. Encouragingly, patients treated with tea tree oil experienced fewer side-effects.[10]
The present study, till now, is the only double-blind study for the evaluation of tea tree oil for mild to moderate acne vulgaris. We found a six-week course of 5% tea tree oil to be effective in reducing both inflammatory and non-inflammatory acne lesions. This effect was possibly due to the anti-inflammatory and antibacterial effects of the tea tree oil.[15],[16] The low and minimal side-effects of this treatment render it as a suitable treatment option for mild to moderate acne vulgaris.
Considering the broad-spectrum antibacterial activity of tea tree oil, we suggest that its efficacy can be evaluated in cases of acne vulgaris resistant to conventional therapies. Since there are no reports of its teratogenicity,[18] we suggest that its safety should be examined in pregnancy.
| Acknowledgement | | |
We thank Drs. DJahed, Asilian, Shariati, Enshaieh, Fatemi, Faghihi and Vali and especially Cinere company for their help in performing this research.
| References | | |
| 1. | White GM. Recent findings in the epidemiologic evidence, classification and subtypes of acne vulgaris. J Am Acad Dermatol 1998;39:S34-7.  [PUBMED] [FULLTEXT] |
| 2. | The social impact of acne. American Academy of Dermatology. [cited on 2006 Feb]. 2002: 46. Available from: http://www.skincarephysicians.com/acnenet/socimpact.html. |
| 3. | Leyden JJ. Antibiotic resistant acne. Cutis 1976;17:593-6. [PUBMED] |
| 4. | Leyden JJ, McGinley KJ, Cavalieri S, Webster GF, Mills OH, Kligman AM. Propionibacterium acnes resistance to antibiotics in acne patients. J Am Acad Dermatol 1983;8:41-5. [PUBMED] |
| 5. | Eady EA, Cove JH, Holland KT, Cunliffe WJ. Erythromycin resistant propionibacteria in antibiotic treated acne patients: Association with therapeutic failure. Br J Dermatol 1989;121:51-7. [PUBMED] |
| 6. | Eady EA, Jones CE, Tipper JL, Cove JH, Cunliffe WJ, Layton AM. Antibiotic resistant propionibacteria in acne: Need for policies to modify antibiotic usage. BMJ 1993;306:555-6. [PUBMED] [FULLTEXT] |
| 7. | Carson CF, Riley TV. Antimicrobial activity of the essential oil of Melaleuca alternifolia . Lett Appl Microbiol 1993;16:49-55. |
| 8. | Brand C, Ferrante A, Prager RH, Riley TV, Carson CF, Finlay-Jones JJ, et al . The water soluble components of the essential oil of Melaleuca alternifolia (tea tree oil), suppress the production of superoxide by human monocytes, but not neutrophils, activated in vitro . Inflamm Res 2001;50:213-9. |
| 9. | Koh KJ, Pearce AL, Marshman G, Finlay-Jones JJ, Hart PH. Tea tree oil reduces histamine-induced skin inflammation. Br J Dermatol 2002;147:1212-7. [PUBMED] [FULLTEXT] |
| 10. | Bassett IB, Pannowitz DL, Barnetson RS. A comparative study of tea-tree oil versus benzoylperoxide in the treatment of acne. Med J Aust 1990;153:455-8. [PUBMED] |
| 11. | Raman A, Weir U, Bloomfield SF. Antimicrobial effects of tea-tree oil and its major components on Staphylococcus aureus, Staphylococcus epidermidis and Propionibacterium acnes. Lett Appl Microbiol 1995;21:242-5. [PUBMED] |
| 12. | Cunliffe W, Gollnick H PM. Topical Therapy. In : Cunliffe W, Gollnick HP, editors. Acne diagnosis and management. Martin Dunitz Press: USA; 2001. p. 107-14. |
| 13. | Brophy JJ, Davies NW, Southwell IA, Stiff IA, Williams LR. Gas chromatographic quality control for oil of Melaleuca terpinen-4-ol type (Australian tea tree). J Agric Food Chem 1989;37: 1330-5. |
| 14. | International Organization for Standardization. Essential oils-oil of Melaleuca, terpinen-4-ol type (tea tree oil). ISO-4730. Geneva, Switzerland; 1996. |
| 15. | Concha JM, Moore LS, Holloway WJ. Antifungal activity of Melaleuca alternifolia (tea tree) oil against various pathogenic organisms. Podiatr Med Assoc 1998;88:489-92. [PUBMED] [FULLTEXT] |
| 16. | Nenoff P, Haustein UF, Brandt W. Antifungal activity of the essential oil of Melaleuca alternifolia (tea tree oil) against pathogenic fungi in vitro . Skin Pharmacol 1996;9:366-94. [PUBMED] |
| 17. | Jandourek A, Vaishampayan JK, Vazquez JA. Efficacy of Melaleuca oral solution for the treatment of fluconazole refractory oral candidiasis in AIDS patients. AIDS 1998;12:1033-7. [PUBMED] [FULLTEXT] |
| 18. | Evandri MG, Battinelli L, Daniele C, Mastrangelo S, Bolle P, et al . The antimutagenic activity of Lavandula angustifolia (lavender) essential oil in the bacterial reverse mutation assay. Food Chem Toxicol 2005;43:1381-7. |
Figures
[Figure - 1], [Figure - 2] Tables
[Table - 1]
| This article has been cited by | | 1 |
Guidelines of care for the management of acne vulgaris |
|
| Andrea L. Zaenglein,Arun L. Pathy,Bethanee J. Schlosser,Ali Alikhan,Hilary E. Baldwin,Diane S. Berson,Whitney P. Bowe,Emmy M. Graber,Julie C. Harper,Sewon Kang,Jonette E. Keri,James J. Leyden,Rachel V. Reynolds,Nanette B. Silverberg,Linda F. Stein Gold,Megha M. Tollefson,Jonathan S. Weiss,Nancy C. Dolan,Andrew A. Sagan,Mackenzie Stern,Kevin M. Boyer,Reva Bhushan | | Journal of the American Academy of Dermatology. 2016; | | [Pubmed] | [DOI] | | | 2 |
Development, optimization, and characterization of a novel tea tree oil nanogel using response surface methodology |
|
| Priyam Sinha,Shruti Srivastava,Nidhi Mishra,Dhananjay Kumar Singh,Suaib Luqman,Debabrata Chanda,Narayan Prasad Yadav | | Drug Development and Industrial Pharmacy. 2016; : 1 | | [Pubmed] | [DOI] | | | 3 |
Medicinal Plants for the Treatment of Acne Vulgaris: A Review of Recent Evidences |
|
| Hamid Nasri,Mahmoud Bahmani,Najmeh Shahinfard,Atefeh Moradi Nafchi,Shirin Saberianpour,Mahmoud Rafieian Kopaei | | Jundishapur Journal of Microbiology. 2015; 8(11) | | [Pubmed] | [DOI] | | | 4 |
Laboratory Evaluation of Safety and Efficacy for Melafix (Melaleuca cajuputi Extract) |
|
| Raghunath B. Shivappa,Larry S. Christian,Edward J. Noga,Jerry M. Law,Gregory A. Lewbart | | Journal of Exotic Pet Medicine. 2015; 24(2): 188 | | [Pubmed] | [DOI] | | | 5 |
Alternative Medicine in Pediatric Dermatology: What Is the Evidence? |
|
| Mark A. Strom,Peter A. Lio | | Current Dermatology Reports. 2014; 3(4): 165 | | [Pubmed] | [DOI] | | | 6 |
New Perspectives on Antiacne Plant Drugs: Contribution to Modern Therapeutics |
|
| Priyam Sinha,Shruti Srivastava,Nidhi Mishra,Narayan Prasad Yadav | | BioMed Research International. 2014; 2014: 1 | | [Pubmed] | [DOI] | | | 7 |
Botanical and Phytochemical Therapy of Acne: A Systematic Review |
|
| Whitney A. Fisk,Hadar A. Lev-Tov,Raja K. Sivamani | | Phytotherapy Research. 2014; : n/a | | [Pubmed] | [DOI] | | | 8 |
Treatment of acne with tea tree oil (melaleuca) products: A review of efficacy, tolerability and potential modes of action |
|
| K.A. Hammer | | International Journal of Antimicrobial Agents. 2014; | | [Pubmed] | [DOI] | | | 9 |
Epidemiology and Management of Acne in Adult Women |
|
| Whitney A. Fisk,Hadar A. Lev-Tov,Raja K. Sivamani | | Current Dermatology Reports. 2014; | | [Pubmed] | [DOI] | | | 10 |
A review of applications of tea tree oil in dermatology |
|
| Nader Pazyar,Reza Yaghoobi,Nooshin Bagherani,Afshin Kazerouni | | International Journal of Dermatology. 2013; 52(7): 784 | | [Pubmed] | [DOI] | | | 11 |
α-Terpinene, an Antioxidant in Tea Tree Oil, Autoxidizes Rapidly to Skin Allergens on Air Exposure |
|
| Johanna Rudbäck, Moa Andresen Bergström, Anna Börje, Ulrika Nilsson, Ann-Therese Karlberg | | Chemical Research in Toxicology. 2012; 25(3): 713 | | [VIEW] | [DOI] | | | 12 |
Harnessing the Power of Crowds |
|
| April W. Armstrong,Safia Cheeney,Julie Wu,Caitlin T. Harskamp,Clayton W. Schupp | | American Journal of Clinical Dermatology. 2012; 13(6): 405 | | [Pubmed] | [DOI] | | | 13 |
A review of phytotherapy of acne vulgaris: Perspective of new pharmacological treatments |
|
| Hanieh Azimi,Mehrnaz Fallah-Tafti,Ali Asghar Khakshur,Mohammad Abdollahi | | Fitoterapia. 2012; 83(8): 1306 | | [Pubmed] | [DOI] | | | 14 |
Plant essential oils and their constituents in coping with multidrug-resistant bacteria |
|
| Kateryna Volodymyrivna Kon,Mahendra Kumar Rai | | Expert Review of Anti-infective Therapy. 2012; 10(7): 775 | | [Pubmed] | [DOI] | | | 15 |
Acne vulgaris |
|
| Hywel C Williams, Robert P Dellavalle, Sarah Garner | | The Lancet. 2011; | | [VIEW] | [DOI] | | | 16 |
The Art and Science of New Advances in Cosmeceuticals |
|
| Zoe Diana Draelos | | Clinics in Plastic Surgery. 2011; | | [VIEW] | [DOI] | | | 17 |
Different approaches of alternative medicines in acne vulgaris treatment |
|
| V. K. Ghosh,D. H. Nagore,K. P. Kadbhane,M. J. Patil | | Oriental Pharmacy & Experimental Medicine. 2011; 11(1): 1 | | [Pubmed] | [DOI] | | | 18 |
Microencapsulation of <i>Melaleuca alternifolia</i> (Tea Tree) Oil as Biocide for Footwear Applications |
|
| M. Magdalena Sánchez-Navarro, Natalia Cuesta-Garrote, Francisca Arán-Aís, César Orgilés-Barceló | | Journal of Dispersion Science and Technology. 2011; 32(12): 1722 | | [VIEW] | [DOI] | | | 19 |
More evidence is needed to confirm the benefits and risks of many botanicals in dermatology |
|
| [No author name available] | | Drugs and Therapy Perspectives. 2011; 27(7): 24-26 | | [Pubmed] | | | 20 |
Topical herbal remedies: Research opportunities for plastic surgeons |
|
| Aleksandra Krajewski,Manish Garg,Rajiv Y. Chandawarkar | | Journal of Plastic, Reconstructive & Aesthetic Surgery. 2010; 63(6): 896 | | [Pubmed] | [DOI] | | | 21 |
Which plant for which skin disease? Part 1: Atopic dermatitis, psoriasis, acne, condyloma and herpes simplex : Which plant for which skin disease? |
|
| Juliane Reuter, Ute Wölfle, Steffi Weckesser, Christoph Schempp | | JDDG Journal der Deutschen Dermatologischen Gesellschaft. 2010; 8(10): 788 | | [VIEW] | [DOI] | | | 22 |
Botanicals in Dermatology : An Evidence-Based Review |
|
| Juliane Reuter, Irmgard Merfort, Christoph M. Schempp | | American Journal of Clinical Dermatology. 2010; 11(4): 247 | | [VIEW] | [DOI] | | | 23 |
Topical herbal remedies: Research opportunities for plastic surgeons |
|
| Krajewski, A., Garg, M., Chandawarkar, R.Y. | | Journal of Plastic, Reconstructive and Aesthetic Surgery. 2010; 63(3): 896-905 | | [Pubmed] | | | 24 |
Adjunctive acne therapies - 2010 | [Ergänzende verfahren in der aknetherapie - Aktualisierung 2010] |
|
| Degitz, K., Plewig, G., Gollnick, H. | | JDDG - Journal of the German Society of Dermatology. 2010; 8(sup 1): 75-80 | | [Pubmed] | | | 25 |
Update on the treatment of acne vulgaris |
|
| Lai, K.W., Mercurio, M.G. | | Journal of Clinical Outcomes Management. 2009; 16(3): 115-126 | | [Pubmed] | | | 26 |
Novel vesicular and particulate drug delivery systems for topical treatment of acne |
|
| Castro, G.A., Ferreira, L.A.M. | | Expert Opinion on Drug Delivery. 2008; 5(6): 665-679 | | [Pubmed] | | | 27 |
Biological effects of essential oils - A review |
|
| Bakkali, F., Averbeck, S., Averbeck, D., Idaomar, M. | | Food and Chemical Toxicology. 2008; 46(2): 446-475 | | [Pubmed] | | | 28 |
Novel vesicular and particulate drug delivery systems for topical treatment of acne |
|
| Gisele A Castro,Lucas AM Ferreira | | Expert Opinion on Drug Delivery. 2008; 5(6): 665 | | [Pubmed] | [DOI] | | | 29 |
Biological effects of essential oils – A review |
|
| F. Bakkali,S. Averbeck,D. Averbeck,M. Idaomar | | Food and Chemical Toxicology. 2008; 46(2): 446 | | [Pubmed] | [DOI] | |
|
|
|
|
|
|
|
|
