Renova Retin-A
Liposomes as carriers for dermal delivery of tretinoin: in vitro evaluation of drug permeation and vesicle-skin interaction.

Sinico C, Manconi M, Peppi M, Lai F, Valenti D, Fadda AM.

Dipartimento Farmaco Chimico Tecnologico, Universita di Cagliari, Via Ospedale 72, 09124 Cagliari, Italy.

The influence of liposome composition, size, lamellarity and charge on the (trans)dermal delivery of tretinoin (TRA) was studied. For this purpose we studied both multilamellar (MLV) or unilamellar (UV) liposomes. Positively or negatively charged liposomes were obtained using either hydrogenated (Phospholipon(R)90H) or non-hydrogenated soy phosphatidylcholine (Phospholipon(R)90) and cholesterol, in combination with stearylamine or dicetylphosphate. Liposomal formulations were characterized by transmission electron microscopy (TEM) and optical and light polarized microscopy for vesicle formation and morphology, and by dynamic laser light scattering for size distribution. In order to obtain more information about the stability and the thermodynamic activity of the liposomal tretinoin, TRA diffusion through a lipophilic membrane was investigated. The effect of the vesicular incorporation of tretinoin on its accumulation into the newborn pig skin was also studied. The experiments were performed in vitro using Franz cells in occlusive conditions and were compared to three different controls. The tretinoin amount delivered through and accumulated in the several skin layers was detected by HPLC. Furthermore, TEM in combination with osmium tetroxide was used to visualize the skin structure after the liposomal administration. Overall obtained results showed that liposomes may be an interesting carrier for tretinoin in skin disease treatment, when appropriate formulations are used. In particular, negatively charged liposomes strongly improved newborn pig skin hydration and TRA retention, though no evidence of intact vesicle penetration was found.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15710506&dopt=Abstract tretinoin Retin-A Renova



Renova Retin-A
Niosomes as carriers for tretinoin. II. Influence of vesicular incorporation on tretinoin photostability.

Manconi M, Valenti D, Sinico C, Lai F, Loy G, Fadda AM.

Dipartimento Farmaco Chimico Tecnologico, Via Ospedale 72, 09124 Cagliari, Italy.

In this work, we compared the chemical stability of tretinoin (TRA) in methanol and in vesicular suspensions exposed both to UV and artificial daylight conditions with the aim of evaluating the potential of niosomes as topical carriers capable of improving the stability of photosensitive drugs. Tretinoin-loaded niosomes were prepared from polyoxyethylene (4) lauryl ether (Brij 30), sorbitan esters (Span 40 and Span 60) and a commercial mixture of octyl/decyl polyglucosides (Triton CG110). Liposomes made from hydrogenated (P90H) and non-hydrogenated (P90) soy phosphatidylcholines were also prepared and studied. In order to evaluate the influence of vesicle structure on the photostability of tretinoin, TRA-loaded vesicles were prepared by the film hydration method, extrusion technique and sonication. After UV irradiation, TRA dissolved in methanol degraded very quickly while the incorporation in vesicles always led to a reduction of the photodegradation process. The photoprotection offered by vesicles varied depending on the vesicle structure and composition. After fluorescent light irradiation for 21 days, not all the studied vesicular formulations improved TRA stability when compared with the free drug in methanol. Tretinoin incorporated in P90 or Span vesicles presented a half-life shorter or very close to that of the free drug. However, the inclusion of TRA in P90H liposomes and Brij 30 or Triton CG110 niosomes retarded the drug photodegradation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12842345&dopt=Abstract tretinoin Retin-A Renova



Renova Retin-A
Topical chemoprevention of oral cancer with tretinoin "biofilm".

Wang Z, Polavaram R, Fuentes CF, Shapshay SM.

Department of Otolaryngology-Head and Neck Surgery, Boston Medical Center/Boston University School of Medicine, Boston, Mass, USA. zwang bu.edu

BACKGROUND: Oral cancer is a common malignancy. Chemoprevention is a promising treatment strategy but it produces systemic toxic effects. Topical application of chemopreventive agents is an attractive alternative that reduces toxic effects. This study is based on the hypothesis that topical application of mucosal adhesive film (MAF), as a means to deliver tretinoin, is effective and safe for oral cancer chemoprevention. SETTING: Randomized animal study conducted at the Boston University School of Medicine. DESIGN: This study uses the hamster cheek-pouch model to test efficacy and safety of the MAF/tretinoin patch for oral cancer prevention. The oral mucosa of 36 hamsters was painted with dimethylbenzanthracene to produce premalignant lesions. The 36 hamsters were divided into 3 groups of 12 hamsters each as follows: (1) control, no treatment; (2) systemic tretinoin (5.0 mg/kg per day, intraperitoneally); and (3) topically applied MAF/tretinoin patch (0.45 mg tretinoin/cm2, once daily). Treatments continued for 40 days. MAIN OUTCOME MEASURES: Tumor growth and burden were measured over time. The duration of MAF patch retention on mucosa and local tissue reaction to the treatment were also evaluated. RESULTS: The patch stayed on the mucosa for at least 5 hours with no evidence of inflammatory or other adverse reactions from the treated tissue. There was a significant difference in the tumor growth measurement between the control and systemic tretinoin groups (P<.001), and between the control and MAF patch groups (P<.001). CONCLUSIONS: This is the first study, to our knowledge, to use a polymer MAF technique for oral cancer prevention. The MAF/tretinoin patch is safe and effective for such chemoprevention in the hamster model.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12925347&dopt=Abstract tretinoin Retin-A Renova



Renova Retin-A
Effect of topical tretinoin, chemical peeling and dermabrasion on p53 expression in facial skin.

El-Domyati MM, Attia SK, Saleh FY, Ahmad HM, Gasparro FP, Uitto JJ.

Department of Dermatology, Faculty of Medicine, Al-Minya University, Cairo, Egypt. m_domyati hotmail.com

The tumour suppressor protein p53 is a phosphoprotein that is activated by DNA damage. It is involved in the decision whether the cells should stop replication and proceed to repair their DNA, or to die by apoptosis. In the present study, we evaluate the effect of some treatment modalities on the expression of p53 in facial skin. Biopsy specimens were obtained from the facial skin of 20 patients before and after treatment using topical tretinoin (11 cases), TCA chemical peeling (5 cases) and dermabrasion (4 cases). Biopsy specimens were also obtained from 12 control subjects representing the same age groups of the patients. Topical tretinoin therapy was found to induce a significant decrease in the expression of p53 up to 6 months of therapy followed by a significant increase after 10 months of therapy. On the contrary, superficial TCA peeling did not induce any statistically significant change in the expression of p53. On the other hand dermabrasion was found to induce a significant decrease in the level of expression of p53 in biopsies obtained after complete re-epithelialization followed by a significant increase. These changes in the expression of p53 may play a role in mediating the effects of such treatment modalities on the epidermis, as well as prevention of actinic neoplasia by adjusting any disturbance in the proliferation/apoptosis balance observed in photoaged facial skin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14693485&dopt=Abstract tretinoin Retin-A Renova