ABSTRACT
This work aims to investigate the influence of the formation of ion pairing between all-trans retinoic acid (RA) and a lipophilic amine (stearylamine; STE) on the drug encapsulation efficiency (EE) and stability of solid lipid nanoparticles (SLNs). The SLNs were characterized for EE and size. The EE and particle size were significantly improved and reduced, respectively, when the surfactant or co-surfactant concentration increased. However, while the formulation without STE allowed only 13% of RA encapsulation, the EE for RA-STE-loaded SLNs was 94%. The stability studies showed a significant decrease in EE for the SLNs without STE, while, for SLNs loaded with RA and STE, the EE remained constant after 360 days. The interactions among ion pairing components and the lipid matrix were investigated through small-angle X-ray scattering (SAXS). The SAXS analysis revealed the presence of RA in the crystalline form in SLNs without ion pairing, while crystalline RA was not observed in SLNs loaded with RA/amine. Skin irritation studies showed that the SLNs loaded with the ion pairing were significantly less irritating when compared to the marketed RA-cream. This novel SLN formulation represents a promising alternative for topical treatment of acne with RA.
Subject(s)
Amines/chemistry , Drug Delivery Systems/methods , Excipients/chemistry , Nanoparticles/chemistry , Tretinoin/chemistry , Acne Vulgaris/drug therapy , Administration, Cutaneous , Amines/administration & dosage , Animals , Chemistry, Pharmaceutical/methods , Drug Stability , Electrochemical Techniques , Emulsions/chemistry , Exanthema , Excipients/administration & dosage , Female , Mice , Mice, Hairless , Nanoparticles/administration & dosage , Particle Size , Phase Transition , Scattering, Small Angle , Surface Properties , Surface-Active Agents/administration & dosage , Surface-Active Agents/chemistry , Tretinoin/administration & dosage , Tretinoin/adverse effects , X-Ray DiffractionABSTRACT
BACKGROUND: The efficacy of the antiacne topical drugs is well established. The local side effects, however, mainly cutaneous irritation, erythema, dryness, peeling and scaling, remain major problems. Novel vesicular and particulate drug delivery systems have been proposed to reduce the side effects of drugs commonly used in the topical treatment of acne. OBJECTIVE: This review focuses on the development and evaluation of antiacne drug-loaded vesicular and particulate delivery systems (liposomes, polymeric microspheres and solid lipid nanoparticles) for topical treatment, their advantages and challenges. METHODS: All the literature available was reviewed to highlight the potential of these novel systems for the topical treatment of acne. CONCLUSION: The encapsulation of antiacne drugs in vesicular and particulate delivery systems represents an innovative alternative to minimize side effects, while preserving their efficacy. This can be obtained by the capacity of these systems to provide controlled release or to improve the drug penetration into skin or even into the pilosebaceous unit.
Subject(s)
Acne Vulgaris/drug therapy , Drug Delivery Systems , Administration, Topical , Benzoyl Peroxide/administration & dosage , Clindamycin/administration & dosage , Clinical Trials as Topic , Drug Stability , Humans , Imidazoles/administration & dosage , Liposomes , Microspheres , Nanoparticles , Nitriles/administration & dosage , Tretinoin/administration & dosageABSTRACT
The development of solid lipid nanoparticles (SLN) containing all-trans retinoic acid (RA) is an interesting approach to topical treatment of acne. SLN has potential for controlled release and follicular penetration, which can reduce adverse effects in comparison with conventional formulations. However, the encapsulation efficiency (EE) of RA in SLN is usually low, unless a high surfactant/lipid ratio is used. The aim of this work was to develop SLN with high EE using a low surfactant/lipid ratio. Different formulations of RA-loaded SLN were prepared using glyceryl behenate as lipid matrix. The particle size, EE, zeta potential and differential scanning calorimetry (DSC) were investigated. High EE in SLN was obtained with addition of amines. These results indicate that the utilization of amines is an interesting approach to improve the EE of RA in SLN using a low surfactant/lipid ratio.
