Novel nanocarriers for the bioactive natural products alkannins for topical use

Nanocarriers, such as liposomes, niosomes and nanoemulsions are extensively investigated drug delivery systems (DDS) for lipophilic and hydrophilic drugs [1]. Alkannins and shikonins (A/S) are naturally occurring hydroxynaphthoquinones with a well-established spectrum of wound healing, regenerative, antimicrobial, anti-inflammatory, antioxidant and antitumor activities [2]. Our group has successfully developed and characterized liposomal DDS of A/S using several phospholipids [3]. The aim of the present study was to prepare and characterize novel nanocarriers containing a mixture of alkannin and its derivatives (API) isolated as in [4] from the hexane extract of Alkanna tinctoria roots, using PHOSAL^® 40IP (kindly donated by Lipoid GmbH, Ludwigshafen, Germany), by the reverse phase evaporation technique [5]. PHOSAL^® contain soybean phosphatidylcholine in sunflower oil and can be used as carriers for lipophilic and amphiphilic APIs. In order to optimize the formulation, different ratios of PHOSAL:cholesterol (10:1, 6.5:1 and 3:1 w/w) and PHOSAL:drug (40:1, 22.5:1 and 5:1 w/w) were examined, monitoring the particle size distribution, ζ-potential values, entrapment efficiency and drug release. The prepared formulations exhibited mean particle size from 120–200 nm, PDI values ranging between 0.117–0.269 and ζ-potential ones ranging from − 11 to − 18 mV. Furthermore, the API loading ranged between 3.12–5.98%, while entrapment efficiency reached 70%. The in vitro release was measured at phosphate buffer saline (pH 5.5 with 1% SDS) using UV spectrophotometry at 519 nm, as shown in [Fig. 1]. These findings are considered promising and could be used for further design of dermal nanocarriers using PHOSAL^® 40 IP.

Fig. 1 Release profile of APIs from different samples (519 nm).

• References

• 1 Demetzos C, Pippa N. Advanced drug delivery nanosystems (aDDnSs): A mini-review. Drug Deliv 2014; 21 (04) : 250-257.
• 2 Papageorgiou VP, Assimopoulou AN, Couladouros EA. et al. The chemistry and biology of alkannin, shikonin and related naphthazarin natural products. Angew Chem Int Ed 1999; 38: 270-300.
• 3 Kontogiannopoulos KN, Dasargyri A, Ottaviani MF. et al. Advanced Drug Delivery Nanosystems for Shikonin: A Calorimetric and Electron Paramagnetic Resonance Study. Langmuir 2018; 34 (32) : 9424-9434.
• 4 Assimopoulou AN, Papageorgiou VP. Study on the enantiomeric ratio of the pharmaceutical substances alkannin and shikonin. Biomed Chromatogr 2004; 18: 791-799.
• 5 Szoka F, Papahadjopoulos D. Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation. Proc Natl Acad Sci USA 1978; 75: 4194-4198.