Aminolevulinic acid-loaded Witepsol microparticles manufactured using a spray congealing procedure: implications for topical photodynamic therapy

Abstract

Objectives The aim was to enhance aminolevulinic acid (ALA) stability by incorporation into low-melting microparticles prepared using a spray congealing procedure and to evaluate temperature-triggered release, allowing topical bioavailability following melting at skin temperature. Methods ALA-loaded Witepsol microparticles were prepared using a novel spray congealing technique. Entrapment efficiency was compared with conventional emulsionbased methods and modelled drug release profiles determined using a membrane separation technique. Raised receiver medium temperature was used to determine triggered release. Bioavailability and lipid-mediated enhancement of ALA penetration were determined in excised murine skin. Key findings ALA-loaded Witepsol microparticles were spherical, with a mean diameter of 20 mm. Loading and stability studies demonstrated effective encapsulation, ranging from 91% to 100%, with no evidence of degradation to pyrazine derivatives. ALA release correlated with dissolution medium temperature, triggered at temperatures close to that of skin. Results suggested that molten Witepsol enhanced cutaneous permeation, whereas incorporation of microparticles in a semi-solid vehicle attenuated ALA penetration. Optimal use was direct application under occlusion. Conclusions Spray congealing is superior to the emulsion-based procedures with respect to encapsulation efficiency of ALA in Witepsol matrices, providing temperature-triggered release, enhanced stability and improved penetration of ALA through keratinised skin. These features could improve ALA delivery to superficial lesions as part of photodynamic therapy.

Encapsulation via Spray Chilling/Cooling/Congealing

“…Researchers have been using ethanol-water mixtures (64% v/v), aqueous solutions of surfactants, silicon oil, Triton X-100 solution in 1% deionized water (weight/volume), ethanol 96% and isobutanol. Besides, the sample is also sonicated (Al-Kassas et al, 2009;Passerini et al, 2012).…”

“…Normally, a given amount of particles are suspended in a buffer (borate pH 5.0; phosphate pH 6.8; and phosphate pH 7.4) added of sodium azide, and the mixture is incubated at 37°C for many days (Maschke et al, 2007;Al-Kassas et al, 2009;Ilic et al, 2009). …”

Photonanodermatology: the interface of photobiology, dermatology and nanotechnology

“…There is a tremendous potential for nanoparticledriven drug delivery, which has led to a huge swell of interest in this area. The many advantages of nanovehicles include their small size, customizable surface properties, tunable solubility, and multifunctionality (2,(65)(66)(67)(68)(69)(70)(71)(72)(73). They pave the way for new ground to break in biomedical applications.…”

Influence of formulation factors on PpIX production and photodynamic action of novel ALA‐loaded microparticles

“…The gel formulation performed slightly better once again, reducing the tumour growth rate by approximately 105%, compared with the 89% reduction achieved using particles alone. Following the promising results obtained in this study, work is now going on to prepare particle-loaded gels under GMP conditions with the aim of initiating an exploratory clinical trial.Witepsol s H15 microparticles containing defined ALA loadings (1% w/w, 2% w/w, 3% w/w, 5% w/w and 10% w/w) were prepared by the spray congealing method described previously [22,23]. Briefly, compressed air, running at 90 p.s.i., was piped through a coiled heat exchanger device R. F. DONNELY ET AL.…”

“…Witepsol s H15 microparticles containing defined ALA loadings (1% w/w, 2% w/w, 3% w/w, 5% w/w and 10% w/w) were prepared by the spray congealing method described previously [22,23]. Briefly, compressed air, running at 90 p.s.i., was piped through a coiled heat exchanger device R. F. DONNELY ET AL.…”