Safety Assessment of Tretinoin Loaded Nano Emulsion and Nanostructured Lipid Carriers: A Non-invasive Trial on Human Volunteers (original) (raw)
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Solid lipid nanoparticles (SLN) of tretinoin: Potential in topical delivery
International Journal of Pharmaceutics, 2007
The objective of this investigation was to develop solid lipid nanoparticles (SLN) of tretinoin (TRE) with the help of facile and simple emulsification-solvent diffusion (ESD) technique and to evaluate the viability of an SLN based gel in improving topical delivery of TRE. The feasibility of fabricating SLN of TRE by the ESD method was successfully demonstrated in this investigation. The developed SLN were characterized for particle size, polydispersity index, entrapment efficiency of TRE and morphology. Studies were carried out to evaluate the ability of SLN in improving the photostability of TRE as compared to TRE in methanol. Encapsulation of TRE in SLN resulted in a significant improvement in its photostability in comparison to methanolic TRE solution and also prevented its isomerization. Furthermore, the skin irritation studies carried out on rabbits showed that SLN based TRE gel is significantly less irritating to skin as compared to marketed TRE cream and clearly indicated its potential in improving the skin tolerability of TRE. In vitro permeation studies through rat skin indicated that an SLN based TRE gel has permeation profile comparable to that of the marketed TRE cream.
Archives of Dermatological Research, 2021
Here, we assessed the efficacy and safety of Nano lipid carrier (NLC) drug delivery system containing tretinoin (NLC-TRE) in comparison with the conventional 0.05% tretinoin cream (TRE cream) in mild to moderate acne vulgaris. A stable and appropriate NLC-TRE formulation was prepared using a high-pressure homogenizer and particle characterization and physicochemical properties were evaluated under accelerated conditions. Efficacy assessment was performed via a split-face clinical study, by comparing the number of acne lesions, porphyrin production and skin biophysical parameters in both sides of the face randomly treated with NLC-TRE and TRE cream. Plasma concentration of tretinoin after topical application of NLC-TRE was measured for primary safety evaluation. We acquired a stable, spherical nanoparticles with particle size of 118.5 nm, PI equal to 0.485 and ZP of − 44.7 mV. The rate of decrease of acne lesions was significantly higher in NLC- TRE side (p value < 0.001). The siz...
In vitro comparison of simple tretinoin-cream and cream loaded with tretinoin-SLN
Background: Tretinoin is one of the commonly used medications in treatment of skin aging symptoms. However, its topical application leads to local irritation at the application site which often limits its tolerability by patients. Solid lipid nanoparticles (SLN) have been developed as an alternative carrier system to emulsions with several advantages such as possibility of controlled drug release, drug targeting and increased drug stability. Methods: In this study, we formulated SLN with hot high pressure homogenization technique. For all formulations the lipid phase was dispersed in water containing 1- 3% nonionic surfactant at 75°C and a premix was formed by homogenizing in an IKA Ultra Turrax high-speed stirrer followed by an IKA high pressure homogenizer. We applied 3, 5, 7 and 9 cycles at pressure range of 250-1000 bars. The z-average and zeta potential was analyzed by Malvern Zetasizer ZEN 3600. Results: The property of the particles depends on the amount of surfactant, production pressure and the number of homogenization cycles. The best formulation which was stable for two years contained 10% cetyl palmitate as a lipid, 2% tego care 450 as a surfactant and 88% water at 1000 bars (5 cycles) with z-average of 140±5 nm. Conclusion: The in vitro release studies showed that SLN containing tretinoin has prolonged profile as compared to commercially available tretinoin creams. It appears that the prolong release profile sustains permeation and absorption of tretinoin and also provides skin tolerability.
Nanoemulsion System for Topical Delivery of Tretinoin
2015
The objective of the present study is to formulate and investigate the potential of nanoemulsion formulation for topical delivery of tretinoin. Tretinoin nanoemulsion was prepared by using Phase Inversion Composition Method. In vitro drug release profile through pig skin was studied using Franz diffusion cell. The skin retention studies showed better retention of drug in the tissue as compared to controls. Tretinoin nanoemulsion with droplet size in the range of 20-200 nm showed effective antiacne activity against Staphylococcus epidermidis. These results suggested that nanoemulsions are potential vehicles for improved topical delivery of tretinoin.
Pharmaceutical Nanotechnology, 2015
Cosmetic skin care products currently in the market demonstrate an increasing trend towards antiaging products. Selection of the right formulation approach is the key to successful consumer acceptance. Nanostructured lipid carriers (NLCs) for dermal application can render added benefits to the formulation. Tretinoin a derivative of vitamin A, is a retinoid with antiaging and anti-acne potential. The present study was aimed at formulating NLCs of tretinoin for reducing the skin irritation potential, increasing the drug loading capacity and prolonging the duration of action. The NLCs were optimized using the response surface methodology based on the particle size. Preliminary study, suggested the use of stearic acid, oleic acid, Tween 80 and Span 60 as solid lipid, liquid lipid and surfactants respectively formed a stable dispersion. NLCs of tretinoin were prepared by hot melt microemulsion and hot melt probe sonication methods. The properties of the optimized NLCs such as morphology, size, Zeta potential, stability and in vitro drug release were investigated. Tretinoin loaded NLCs in carbopol gel showed a sustained release pattern with isopropyl alcohol as the receptor fluid compared to the marketed gel using Franz diffusion cells. Eight prepared gel formulations tested were found to follow the Higuchi model of drug release. Stability studies indicated that the formulations stored at refrigeration and room temperature showed no noticeable differences in the drug content and release profiles in vitro, after a period of 4 weeks. In vivo skin irritation test on male Wister rats indicated no irritation or erythema after application of the NLCs loaded gel repeated for a period of 7 days compared to the application of marketed tretinoin gel which showed irritation and slight erythema within 3 days. The results showed that the irritation potential of tretinoin was reduced, the drug loading was increased and the drug release was prolonged by the incorporation into the NLCs.
International Journal of Pharmaceutics, 2014
The aim of this study was to develop biocompatible lipid-based nanocarriers for retinyl palmitate (RP) to improve its skin delivery, photostability and biocompatibility, and to avoid undesirable topical side effects. RP loaded nanoemulsions (NEs), liposomes (LPs) and solid lipid nanoparticles (SLNs) were characterized in terms of size, surface electrical charge, pH, drug encapsulation efficiency and morphology. Spherical-shaped nanocarriers with a negatively charged surface (>|40| mV) and mean size lower than 275 nm were produced with adequate skin compatibility. The rheological properties showed that aqueous dispersions of SLNs followed a non-Newtonian behavior, pseudoplastic fluid adjusted to Herschel-Bulkley equation, whereas LPs and NEs exhibited a Newtonian behavior. SLNs offered significantly better photoprotection than LPs and NEs for RP. The cumulative amount of drug permeated through human skin at the end of 38 h was 6.67 AE 1.58 mg, 4.36 AE 0.21 mg and 3.64 AE 0.28 mg for NEs, LPs and SLNs, respectively. NEs flux was significantly higher than SLNs and LPs: NEs (0.37 AE 0.12 mg/h) > LPs (0.15 AE 0.09 mg/h) > SLNs (0.10 AE 0.05 mg/h). LPs offered significant higher skin retention than NEs and SLNs. Finally, even though all developed nanocarriers were found to be biocompatible, according to histological studies, NE was the system that most disrupted the skin. These encouraging findings can guide in proper selection of topical carriers among the diversity of available lipid-based nanocarriers, especially when a dermatologic or cosmetic purpose is desired.
Chitosan-solid lipid nanoparticles as carriers for topical delivery of tretinoin
Colloids and Surfaces B: Biointerfaces, 2012
Tretinoin (TRE) or all-trans retinoic acid is employed in the topical treatment of various skin diseases including acne and psoriasis. However, its use is strongly limited by side effects and high chemical instability. TRE encapsulation in nanostructured systems reduces these problems. Chitosan is a biopolymer that exhibits a number of interesting properties such as bioadhesion and antibacterial activity. The aim of this work was to prepare and characterize solid lipid nanoparticles (SLN) containing TRE, with and without addition of chitosan, to assess their in vitro cytotoxicity in keratinocytes and to evaluate their antibacterial activity against bacteria related to acne. SLN without (SLN-TRE) and with (SLN-chitosan-TRE) chitosan were prepared by hot high pressure homogenization. The hydrodynamic mean diameter and zeta potential were 162.7 ± 1.4 nm and −31.9 ± 2.0 mV for SLN-TRE, and 284.8 ± 15.0 nm and 55.9 ± 3.1 mV for SLN-chitosan-TRE. The SLN-chitosan-TRE exhibited high encapsulation efficiency, high physical stability in the tested period (one year), were not cytotoxic to keratinocytes and showed high antibacterial activity against P. acnes and S. aureus. Therefore chitosan-SLN can be good candidates to encapsulate TRE and to increase its therapeutic efficacy in the topical treatment of acne.
BioMed Research International, 2021
Cationic nanocapsules represent a promising approach for topical delivery purposes. We elaborated on a novel formulation based on the cationic nanocapsules to enhance the pharmacodynamic efficacy, user compliance, and photostability of tretinoin (TTN). To achieve this goal, TTN nanocapsules were prepared by the nanoprecipitation method. In order to statistically optimize formulation variables, a Box-Behnken design, using Design-Expert software, was employed. Three independent variables were evaluated: total weight of the cationic acrylic polymer (X1), oil volume (X2), and TTN amount (X3). The particle size and encapsulation efficiency percent (EE%) were selected as dependent variables. The optimal formulation demonstrated spherical morphology under scanning electron microscopy (SEM), optimum particle size of 116.3 nm, and high EE% of 83.2%. TTN-loaded nanocapsules improved photostability compared to its methanolic solution. The in vitro release study data showed that tretinoin was r...
European Journal of …, 2011
The aims of this work were to increase the photostability and to reduce the skin permeation of tretinoin through nanoencapsulation. Tretinoin is widely used in the topical treatment of various dermatological diseases such as acne, psoriasis, skin cancer, and photoaging. Tretinoin-loaded lipid-core polymeric nanocapsules were prepared by interfacial deposition of a preformed polymer. Carbopol hydrogels containing nanoencapsulated tretinoin presented a pH value of 6.08 ± 0.14, a drug content of 0.52 ± 0.01 mg g À1 , pseudoplastic rheological behavior, and higher spreadability than a marketed formulation. Hydrogels containing nanoencapsulated tretinoin demonstrated a lower photodegradation (24.17 ± 3.49%) than the formulation containing the non-encapsulated drug (68.64 ± 2.92%) after 8 h of ultraviolet A irradiation. The half-life of the former was seven times higher than the latter. There was a decrease in the skin permeability coefficient of the drug by nanoencapsulation, independently of the dosage form. The liquid suspension and the semisolid form provided K p = 0.31 ± 0.15 and K p = 0.33 ± 0.01 cm s À1 , respectively (p 6 0.05), while the samples containing non-encapsulated tretinoin showed K p = 1.80 ± 0.27 and K p = 0.73 ± 0.12 cm s À1 for tretinoin solution and hydrogel, respectively. Lag time was increased two times by nanoencapsulation, meaning that the drug is retained for a longer time on the skin surface.
Formulation and evaluation of retinyl palmitate and vitamin E nanoemulsion for skin care
Pharmacia
Background: Improving and maintaining the skin integrity and health are the most essential targets in long-term care. The aim of this study is to formulate a serum of retinyl palmitate (RP) and vitamin E (VE) as nanoemulsion (NE) for achieving healthy skin. Methods: The solubility of RP and VE was studied in different oils. The NEs were prepared using oil, water, and different surfactant-co-surfactant mixtures, and then the medicated nanoemulsion was prepared by addition of 0.5% RP and VE to the oil phase, and vitamin C as an antioxidant to the aqueous phase with different preservatives. The prepared NE was characterized in terms of particle size, charge, rheology, diffusion, and irritation to the skin. Results and conclusion: The data showed that the highest solubility of both RP and VE was in safflower oil. Tween 20, Ceteareth 20 with ethanol, PEG 200, and cremophor RH40. This combination was able to produce NE with good integrity and acceptable particle size. The prepared formula...