Tretinoin Loaded Nanoemulsion for Acne Vulgaris: Fabrication, Physicochemical and Clinical Efficacy Assessments

Abstract

Background and Aim: Acne vulgaris is a common inflammatory skin condition which is treated using Tretinoin (TRE), a widely used retinoid. Nano emulations (NEs) are colloidal nano-sized particles that enhance the therapeutic efficacy of TRE and minimize adverse effects. This study is aimed at developing a TRE-loaded NE (NE-TRE) and at assessing the therapeutic effects of the formulation in acne vulgaris lesions, compared to conventional 0.05% TRE emulsion. Method: The high energy emulsification method was used to make NE-TRE. After obtaining stable NE, particle characterization and physicochemical properties were evaluated under accelerated conditions. Conducting a clinical study, we compared the therapeutic effects of NE-TRE and 0.05% TRE emulsion by comparing the number of acne lesions and porphyrin production in both sides of the face. Results and Conclusion: We successfully developed stable nanoparticles. It was a stable oil-in-water emulsion with particle size of about 150 nm, and containing circular and separated particles. In a pilot clinical study, the number of acne lesions as well as the size and intensity of porphyrin production significantly reduced after topical application of NE-TRE. This formula shows proper efficiency and good loading capacity of TRE in the drug delivery system.

Advanced nanomedicines for the treatment of inflammatory diseases

“…• clinical safety of the formulation in humans [159] PEGylated silica -gold nanoshells Photothermolysis (ultrasound 10 sec to 10 W/cm 2 )…”

“… Nanocarrier Active principle Disease Patients and clinical phase Main Results Ref. PEGylated liposomes Prednisolone Illio-femoral atherosclerosis 14 patients, mean age 70 years (± 7 years) the treatment did not reduce arterial wall permeability or inflammation prolonged circulation half-life of prednisolone [ 150 ] PEGylated liposomes Prednisolone Moderate to severe active ulcerative colitis 18 patients (iv administration) 54 weeks after initiation of treatment only 4 patients out of 13 in remission [ 155 ] Liposome Cyclosporine (lipogel or cream) Chronic plaque psoriasis 38 patients (receiving cyclosporine lipogel or conventional cyclosporine cream or placebo 14 weeks after initiation of treatment, complete clearance was observed in lesion sites in 41% patients treated with cyclosporine lipogel and none for patients treated with cyclosporine cream or placebo gel [ 156 ] Glutatione-PEGylated liposomes Methyl prednisolone – Assessment of safety, pharmacokinetics and pharmacodynamics slow release formulation with reduced toxicity and prolonged decrease in the lymphocyte count [ 171 ] PLGA Pitavastatine Healthy volunteers 40 patients, Phase I, iv administration well tolerated no significant adverse response [ 158 ] Nanoemulsion (oil in water emulsion) Tretinoin Acnee vulgaris 10 patients with mild to moderate acnee vulgaris lesions clinical safety of the formulation in humans [ 159 ] PEGylated silica -gold nanoshells Photothermolysis (ultrasound 10 sec to 10 W/cm 2 ) Acnee vulgaris 37 patients efficacy...…”

“…In a very recent pilot clinical study, an oil-in-water nanoemulsion containing all trans- retinoic acid (Tretinoin), showed a good efficiency against acne after topical application [ 159 ]. Similarly, when subjected to focal thermolysis of sebaceous gland by near infrared laser, silica-gold nanoshells (150 nm) coated with PEG, were effective to provide a significant reduction in occurrence and appearance of inflammatory lesions [ 160 ].…”

Recent Advances in the Structural Design of Photosensitive Agent Formulations Using “Soft” Colloidal Nanocarriers

“…Photosensitive nanoformulations are also applied in acne treatment, a common inflammatory skin condition that can cause discomfort and visible, long-lasting scarring [127]. Examples of treatment agents for acne lesions are retinoids, such as tretinoin, efficiently encapsulated in liposomes [102] and nanoemulsions [110]. In clinical studies, the formulations result in a reduced number of acne lesions and improved skin condition with high efficacy.…”

Targeted Topical Delivery of Retinoids in the Management of Acne Vulgaris: Current Formulations and Novel Delivery Systems

“…Ramenelli et al [66] recently reviewed the nano delivery system approaches that have been applied to tretinoin including liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, cyclodextrins and nanostructured polymers. Some examples are described below and other studies are summarized in Table 3 [51,52,67,68,69,70,71]. The earliest work focused on colloidal vesicles including liposomes, niosomes and microsponge/microsphere, which has progressed to a commercially available product, the MDS as described above.…”