Stability of 5-aminolevulinic acid in novel non-aqueous gel and patch-type systems intended for topical application

McCarron, Paul A.; Donnelly, Ryan F.; Andrews, Gavin; Woolfson, A. David

doi:10.1002/jps.20393

Cited by 25 publications

(9 citation statements)

References 25 publications

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“…Results of the present study point to the fact that MNs used prior to application of ALA-containing cream, apart from displaying a tendency of reducing the experienced discomfort, caused a bigger increase in the amount of PpIX produced than when used prior to application of MAL-containing cream. Reduction of concentrations of prodrugs improves stability of the formulations (40). It also reduces costs per treatment and, therefore, makes the treatment available for more patients.…”

Section: Discussionmentioning

confidence: 99%

Microneedle Pre-treatment of Human Skin Improves 5-Aminolevulininc Acid (ALA)- and 5-Aminolevulinic Acid Methyl Ester (MAL)-Induced PpIX Production for Topical Photodynamic Therapy Without Increase in Pain or Erythema

et al. 2010

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Section: Discussionmentioning

confidence: 99%

Microneedle Pre-treatment of Human Skin Improves 5-Aminolevulininc Acid (ALA)- and 5-Aminolevulinic Acid Methyl Ester (MAL)-Induced PpIX Production for Topical Photodynamic Therapy Without Increase in Pain or Erythema

et al. 2010

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“…About 265 mg or 301.4 mg ALAloaded microparticles were applied to the stratum corneum as either a particulate bolus or suspended in a PG gel containing 3% w/w Carbopol 974P NF. [27] The three types of microparticulate formulation and two simple ALA formulations tested were 1 : 10 and 2 : 100 ALA : Witepsol microparticles; 1 : 10 and 2 : 100 ALA Witepsol microparticles suspended in PG gel; 1 : 10 ALA Witepsol microparticles suspended in PG gel containing 20% w/w DMSO; 10% and 2% w/v ALA solution; 10% and 2% ALA suspended in PG gel.…”

Section: Skin Permeation Studiesmentioning

confidence: 99%

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

Al-Kassas¹,

Donnelly²,

McCarron³

2009

j pharm pharmacol

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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.

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“…However, while the selectivity of PpIX accumulation in tumours can be enhanced [18], improving tissue penetration significantly has proved problematic [20,21]. Moreover, we have been unable to achieve pharmaceutically acceptable ALA stability for any longer than 6 months [19]. Interestingly, a number of groups have formulated ALA into particulate dosage forms.…”

Section: Discussionmentioning

confidence: 99%

“…A novel bioadhesive patch was described that delivered a predefined amount of ALA per unit area, improved the efficiency of topical delivery [16], allowed the drug to be successfully delivered to moist areas of the body, such as the female reproductive tract and the lip [17] and enhanced the selectivity of PpIX accumulation in tumours [18]. However, ALA stability [19] and drug penetration into deep lesions [20,21] continue to cause problems.…”

Section: Introductionmentioning

confidence: 99%

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

Donnelly

McCarron

Al-Kassas

et al. 2009

Biopharm & Drug Disp

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A novel 5-aminolevulinic acid (ALA)-containing microparticulate system was produced recently, based on incorporation of ALA into particles prepared from a suppository base that maintains drug stability during storage and melts at skin temperature to release its drug payload. The novel particulate system was applied to the skin of living animals, followed by study of protoporphyrin IX (PpIX) production. The effect of formulating the microparticles in different vehicles was investigated and also the phototoxicity of the PpIX produced using a model tumour.Particles formulated in propylene glycol gels (10% w/w ALA loading) generated the highest peak PpIX fluorescence levels in normal mouse skin. Peak PpIX levels induced in skin overlying subcutaneously implanted WiDr tumours were significantly lower than in normal skin for both the 10% w/w ALA microparticles alone and the 10% w/w ALA microparticles in propylene glycol gels during continuous 12 h applications. Tumours not treated with photodynamic therapy continued to grow over the 17 days of the anti-tumour study. However, those treated with 12 h applications of either the 10% w/w ALA microparticles alone or the 10% w/w ALA microparticles in propylene glycol gel followed by a single laser irradiation showed no growth. 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.

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Stability of 5-aminolevulinic acid in novel non-aqueous gel and patch-type systems intended for topical application

Cited by 25 publications

References 25 publications

Microneedle Pre-treatment of Human Skin Improves 5-Aminolevulininc Acid (ALA)- and 5-Aminolevulinic Acid Methyl Ester (MAL)-Induced PpIX Production for Topical Photodynamic Therapy Without Increase in Pain or Erythema

Microneedle Pre-treatment of Human Skin Improves 5-Aminolevulininc Acid (ALA)- and 5-Aminolevulinic Acid Methyl Ester (MAL)-Induced PpIX Production for Topical Photodynamic Therapy Without Increase in Pain or Erythema

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

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

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