Improved tretinoin photostability in a topical nanomedicine replacing original liquid suspension with spray-dried powder with no loss of effectiveness.

OBJECTIVE: The use of spray-dried powders containing tretinoin-loaded nanocapsules instead of the original liquid suspension, aimed at the preparation of dermatological nanomedicines with improved photostability, was investigated. METHODS: Powders were prepared using lactose as a drying adjuvant. Hydrogels were prepared using two approaches: dispersing Carbopol Ultrez 10 in an aqueous redispersion of the powder or incorporating the powder in previously formed hydrogels. RESULTS AND DISCUSSION: The photodegradation of tretinoin in hydrogels prepared with the powders showed similar half-life times (around 19.5 h) compared to preparations with the original liquid nanocapsules (20.7 ± 1.4 h), regardless of the preparation approach. In addition, the topical nanomedicines prepared with the spray-dried powders presented a significant improvement in tretinoin photostability compared to the formulation containing the non-encapsulated drug. CONCLUSION: This study verified that the addition of the spray-dried powders containing tretinoin-loaded lipid-core nanocapsules to hydrogels did not influence the photoprotection of the drug compared with the preparation procedure using the original liquid suspension.

Spray-dried powders containing tretinoin-loaded engineered lipid-core nanocapsules: development and photostability study.

The influence of the spray-drying process on the ability of engineered lipid-core nanocapsules to protect tretinoin against UV degradation was evaluated. This approach represents a technological alternative to improve the microbiological stability, storage and transport properties of such formulations. Tretinoin-loaded lipid-core nanocapsules or tretinoin-loaded nanoemulsion were dispersed in lactose (10% w/v) and fed in the spray-drier to obtain a solid product (spray-dried powder containing tretinoin-loaded nanocapsules or nanoemulsion--SD-TTN-NCL or SD-TTN-NE, respectively). SD-TTN-NE showed a lower (p < or = 0.05) percentage of encapsulation (89 +/- 1%) compared to SD-TTN-NCL (94 +/- 2%). Redispersed SD-TTN-NCL and SD-TTN-NE showed z-average sizes of 204 +/- 2 nm and 251 +/- 9 nm, which were close to those of the original suspensions (220 +/- 3 nm and 239 +/- 14 nm, respectively). Similar percentage of photodegradation were determined for tretinoin loaded in nanocapsules (26.15 +/- 4.34%) or in the respective redispersed spray-dried powder (28.73 +/- 6.19 min) after 60 min of UVA radiation exposure (p > 0.05). Our experimental design showed for the first time that spray-dried lipid-core nanocapsules are able to protect tretinoin against UVA radiation, suggesting that the drying process did not alter the supramolecular structure of the lipid-core nanocapsules. Such powders are potential intermediate products for the development of nanomedicines containing tretinoin.

Lipid-core nanocapsules as a nanomedicine for parenteral administration of tretinoin: development and in vitro antitumor activity on human myeloid leukaemia cells.

Tretinoin-loaded conventional nanocapsules have showed a significant protection of this drug against UVC radiation. However, this formulation presents a limited stability on storage. We hypothesized that the association of tretinoin to lipid-core nanocapsules could increase the physicochemical stability of such formulations, focusing on the development of a reliable nanomedicine for parenteral administration. However, this advantage should still be accompanied by the known photoprotective effect of conventional polymeric nanocapsules against the exposure of tretinoin to UV radiation. Results showed that tretinoin-loaded lipid-core nanocapsules improved the physicochemical stability of formulations under storage, without changing their ability to protect tretinoin either against UVA or UVC radiation. In addition, the effect of nanoencapsulation on the antiproliferative and differentiation properties of tretinoin was studied on human myeloid leukemia cells (HL60 cells) showing that tretinoin-loaded lipid-core nanocapsules presents a longer antitumor efficiency compared to the free tretinoin. These results allow us to propose the current formulation (tretinoin-loaded lipid-core nanocapsules) as a promising parenteral nanomedicine for the treatment of acute promyelocytic leukaemia.