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Nanoparticles and Herbal Medicine: Fullerene and Phytocreams in the Treatment of Acne vulgaris Khan Usmanghani, Zeeshan Ahmed Sheikh, Kamran Alam, Majid Feroz, Naureen Lalani, Rabia Bashir, Allah Nawaz Herbion Pakistan (Pvt.) Limited Karachi, Pakistan Nanotechnology • A nanometer is a billionth of a meter. • Something only 1/80,000 the width of a human hair. • Nanotechnology is the creation of useful materials, devices, and systems through the manipulation of matter on this miniscule scale. • The factors that govern larger systems do not necessarily apply at the nanoscale. Because nanomaterials have large surface areas relative to their volumes. What is in it for us?? Most animal cells are 10,000 to 20,000 nanometers in diameter. This means that nanoscale devices (less than 100 nanometers) can enter cells and the organelles inside them hence can easily reach the target site and effectively deliver the drug . Background and Naming: In September 1985, Robert F. Curl, Jr., Richard E. Smalley, and Sir Harold W. Kroto discovered fullerene C60 during laser spectroscopy experiments at Rice University. Fullerenes were named after Richard Buckminster Fuller. Hence Buckminster fullerene from Buckmister Fuller . Shorter 'Fullerene‘ - refers to the family of fullerenes and suffix "ene" indicates presence of "double bonds“. What is Fullerene?? Types: Buckyball Clusters Linked Ball & C Chain Dimer Nanotubes Megatubes Different types of Fullerenes have vastly different properties because of structural variations. Types of Carbon nanotubes Two main types of carbon nanotubes: Single-walled nanotubes (SWNTs) consist of a single graphite sheet seamlessly wrapped into a cylindrical tube. Multiwalled nanotubes (MWNTs) comprise an array of such nanotubes (more than one wall) that are concentrically nested with in. What is Fullerene?? Most Efficient Radical Scavenger In Medical World to Date !! Endohedral Fullerenes : • Other atoms can be trapped inside fullerenes to form inclusion compounds known as Endohedral Fullerenes. Fullerene is also known as Super antioxidant because of its strong antioxidant effect which is 172 times as strong as Vitamin C. Factors contributing to anti oxidant activity • Cage Structure – unique spherical deformation imparts High Reactivity. • Electron Acceptor – it can reversibly accept six electrons because its lowest unoccupied molecular orbital is at a low energy level. Electron Acceptor = Reducing agents = Antioxidants Fullerene & Acne Vulgaris Ideas, Inventions and Innovations is dedicated to all science, patents, products and research innovations Acne, also known as acne vulgaris, is a common skin condition that occurs when hair follicles become plugged with oil and dead skin cells and bacteria. It is a disorder of pilosabaceous unit and characterized by pimples (zits) on the face, chest, and back. Acne is the most common skin disorder affecting 40 million to 50 in developing countries. http://www.patient.co.uk/doctor/acne-vulgaris Prevalence Occurrence: 75 - 80% of teenagers and young adults. Age of Onset: Tends to occur in adolescence, when hormones are in a state of flux (prior to the onset of puberty). It may also appear at some point between 11–30 years of age. Gender: Young men are more likely to suffer from more severe and longer lasting forms of acne. Young women are more likely to suffer from intermittent acne caused by hormonal changes associated with their menstrual cycles or from acne caused by cosmetics. Microcomedone Severity of Acne Whitehead. It is filled with skin debris, bacteria, and oil called sebum. Light Characterized by non inflammatory lesions (comedones). A few inflammatory lesions (papules and pustules) may be present (generally less than 10) Moderate Severe More papules and pustules (10–40) and comedones (10–40) present. The trunk may be mildly affected. Occasional nodules and mild scarring may also be present Widespread inflammatory lesions, nodules and scarring present. Usually involving the face, chest and back. Blackhead .It has black appearance and is filled with skin debris, bacteria, and oil called sebum. Topical Treatment Treatment Therapeutic category Side Effects Benzoyl Peroxide bactericidal, keratolytic, Erythema, dryness and itching and anti-inflammatory are usually mild and transient. agent Retinoic acid and derivatives Comedolytic and antiinflammatory properties. Skin irritation, photosensitivity, initially may worsen acne. Topical Antibiotics Bactericidal activity Minor skin irritation depending on vehicle used. Topical Azelaic acid Comedolytic, antibacterial and anti-inflammatory properties. Pruritus, burning, stinging and tingling. Side effects are mild and transient. Examples Therapeutic Objectives Decrease sebaceous gland activity To reduce counts of Propionibacterium acnes bacteria Anti-inflammatory effects to calm red, inflamed skin by inhibiting lipase production by P.acnes Comedolytics to unplug blocked follicles. Dermidoc S.No. Ingredients Common Name Item Code Composition Using Qty. Issuing Qty. 01 Acacia catechu Kattha Sufaid 1945 1.5 gm 02 Zinc Oxide Safaida Kashghari 2039 3.0 gm 03 Cinnamomum camphora Camphor 1832 0.5 gm 04 Apis Mellifera Honey / Shahad 1912 0.5 gm 05 Melaleuca alternifolia Tea tree Oil 2088 1.25 ml 3829 3.6 gm EXCIPIENTS 01 Ethylene Glycol Monostearate 02 Liquid paraffin 1973 2.0 gm 03 Stearic acid 3828 1.5 gm 04 Cetostearyl alcohol 1836 1.175 gm 05 Methyl Paraben 1994 0.25 gm 06 Propyl Paraben 2031 0.05 gm 07 D.I. Water 1863 7.525 ml 08 Propylene glycol 2030 1.25 ml 09 Tween 80 (Polysorbate 80) 4058 0.9 ml 3.5 gm Remarks Prevalence Occurrence: 75 - 80% of teenagers and young adults. Age of Onset: Tends to occur in adolescence, when hormones are in a state of flux (prior to the onset of puberty). It may also appear at some point between 11–30 years of age. Gender: Young men are more likely to suffer from more severe and longer lasting forms of acne. Young women are more likely to suffer from intermittent acne caused by hormonal changes associated with their menstrual cycles or from acne caused by cosmetics. Methodology Method Open trial for clinical efficacy of topical Anti-Acne in treating Acne. Study population : 24 patients (Ages from 23 to 39 years, and the mean age was 30.7 years (standard deviation, 5.3 years). The number of facial papular and pustular lesions ranged from 3 to 22, corresponding to mild or moderate acne (1–20 lesions on half of the face) as defined by the Acne Study Group in Japan. Methodology Number of drugs Test drug Control drug Comparison Fullerene gel Name of the Z Dermidoc Doxycyclin/ Topical Fullerene gel Product Clindamycin+benzoyl peroxide gel Total Patients Duration of Treatment 12 4 to 8 weeks 12 4 to 8 weeks 11 4 and 8 weeks. Test and Control Drugs: Treatment * Level of Improvement * Patient Sex Crosstabulation Patient Sex Male Level of Improvement Treatment Treatment Total Not Improved Test Drug Count % within Treatment 6 85.7% 1 14.3% 7 100.0% Control Drug Count % within Treatment 7 87.5% 1 12.5% 8 100.0% Count % within Treatment 13 86.7% 2 13.3% 15 100.0% Test Drug Count % within Treatment 4 80.0% 1 20.0% 5 100.0% Control Drug Count % within Treatment 2 50.0% 2 50.0% 4 100.0% Count % within Treatment 6 66.7% 3 33.3% 9 100.0% Total Female Improved Total Patients Characteristic Frequency of these clinical manifestations is described in following graph. The therapeutic evaluation was made on the basis of the signs and symptoms of the patients. Graph: Frequency of clinical manifestations Patients Characteristic-Test and Control drugs Graph : Frequency of patients according to severity of Acne vulgaris Results The comparision is drawn with the published work on effectiveness of fullerene gel in treating acne vulgaris. Open trial using a Anti-Acne Cream Dermidoc twice a day; at 6 and 8 weeks. Control Doxycyclin/ Clindamycin+benzoyl peroxide gel Determine the efficacy of different formulation to contgrol acne with skin care benefit. Comparison of Acne Treatment Results 12 Q1 10 Min Median 8 Overall severity of symptoms Max 6 Q3 Baseline (T0) After treatment (T1) 4 Median IQR Median IQR p value 07 4-10 2 1-4 0.001 2 0 T0 T1 Overall severity of symptoms in control group by Wilcoxon Signed Rank Test 12 Q1 10 Min 8 Median 6 Max 4 Q3 Overall severity of symptoms Baseline (T0) After treatment (T1) Median IQR Median IQR p value 06 4-9 2 1-3 0.001 2 0 T0 T1 Graph: Overall improvement in severity of symptoms in Test group by Wilcoxon Signed Rank Test Conclusion Effects of Anti-Acne Dermidoc cream on number of acne lesions and on various skin related parameters were observed. Clinical and experimental data suggest that fullerene can suppress acne by inhibition of neutrophil infiltration and sebum production, possibly through antioxidatve function. In case of fullerene the p value was found p= 0.05, and the p value of Dermidoc and allopathic drugs (Doxycyclin/clindamycin, benzoyl peroxide gel) is p= 0.001. As compared to control drug and fullerene, the Dermidoc has similar efficacy but has skin care benefit. Competitors 1 CEN-G Enhancing Ampoule and CEN-G Enhancing Mask 2 C60 Fullerene Jelly Facial Mask 3 INSPHERE White Riser Essence (Extract) 4 Z Recovery Intensive Repair Balm 5 Anti Aging Lotion with Vitamin C & Fullerene References http://www.patient.co.uk/doctor/acne-vulgaris http://www.uspharmacist.com/content/c/10277/?t=women's_health,otc_ medications http://www.aafp.org/afp/2000/1015/p1823.html http://filipinoeuro.webs.com/apps/forums/topics/show/2974479 http://www.honeygostudio.com/documents/Acnevulgaris.pdf http://www.americanskin.org/resource/acne.php http://dermatology.about.com/od/acne/ss/how_acne_forms_6.htm Thanks