Biodegradable Polymeric Nanocapsules Based on Poly(DL-lactide) for Genistein Topical Delivery: Obtention, Characterization and Skin Permeation Studies

Abstract

The isoflavone genistein (GEN) is a natural product with potential applications for skin cancer treatment and chemoprevention; however its high lipophilicity and chemical instability limits its clinical use. Therefore, attempts towards protecting GEN against degradation and increasing its penetration in the skin might be a valid approach. In this work, GEN loaded-PLA nanocapsules (GEN-NC) were prepared by interfacial deposition of preformed polymer (nanoprecipitation); physicochemical characterization and stability studies for 90 days were conducted. GEN-NC were incorporated into semi-solid formulations and permeation experiments were carried out using porcine ear skin. GEN-NC optimized formulation presented a mean diameter of 139 +/- 7.31 nm, polydispersity index of 0.128 +/- 0.08, encapsulation efficiency of 89.63 +/- 2.27% and drug loading from 0.6 to 1.4 w/w%. Stability studies demonstrated that nanocapsules did not exhibit aggregation during the 90 days of the assay, however, a drop in encapsulation efficiency was observed in the first 10 days. Permeation experiments demonstrated that a higher amount of GEN reaches deeper layers of the skin and increased penetration was achieved when GEN-NC were incorporated in a semi-solid gel formulation, indicating that GEN-NC might be a promising nanocarrier system for skin delivery of GEN.

Improved nonclinical pharmacokinetics and biodistribution of a new PPAR pan-agonist and COX inhibitor in nanocapsule formulation

“…In vivo studies showed that Lyso-7 has high potency within this class of drugs (3 mg/kg) compared to other anti-inflammatory drugs, indomethacin (10 mg/kg), and TZDs, pioglitazone (50 mg/kg) [10,11], which enables the use of such Lyso-7-NC formulation even though the drug payload was not very high (7% wt/wt). However, lower payloads of 0.6-1.4% and 1.3-3% wt/wt were recently reported for genistein PLA NC [28] and hydrophobic phtalocyanine in PLA NC, respectively [17]. Furthermore, similar payload of 4-6% wt/wt was obtained with docetaxel in PLGA NC [29].…”

New Insights Regarding the Potential Health Benefits of Isoflavones

“…Genistein has been extensively studied in different types of cancers cells and cancer animal models [104]. Unfortunately, the low oral bioavailability of genistein [105], due to its high lipophilicity and its extensive metabolism by the phase II enzymes [106], has limited its use in clinical trials [107].…”

Biocompatible and biodegradable nanoparticles for enhancement of anti-cancer activities of phytochemicals

“…De Zampieri et al [112] found that GEN-nanoparticles resulted in a higher amount of GEN accumulation in deeper layers of the skin and GEN-nanoparticles might be a promising nanocarrier system for skin delivery of GEN and skin cancer prevention and treatment. Other studies have demonstrated that nano-GEN demonstrated a sustained release manner, increased GEN uptake by cancer cells and enhanced anti-cancer activities of GEN in different cancer cells [113, 114] .…”