In vitro evaluation of 5-aminolevulinic acid (ALA) loaded PLGA nanoparticles

Abstract

Background: 5-Aminolevulinic acid (ALA) is a prodrug for topical photodynamic therapy. The effectiveness of topical ALA can be limited by its bioavailability. The aim of this study was to develop a novel ALA delivery approach using poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). Methods: A modified double emulsion solvent evaporation method was used to prepare ALA loaded PLGA NPs (ALA PLGA NPs). The characteristics, uptake, protoporphyrin IX fluorescence kinetics, and cytotoxicity of ALA PLGA NPs toward a human skin squamous cell carcinoma cell line were examined. Results: The mean particle size of spherical ALA PLGA NPs was 65.6 nm ± 26 nm with a polydispersity index of 0.62. The encapsulation efficiency was 65.8% ± 7.2% and ALA loading capacity was 0.62% ± 0.27%. When ALA was dispersed in PLGA NPs, it turned into an amorphous phase. ALA PLGA NPs could be taken up by squamous cell carcinoma cells and localized in the cytoplasm. The protoporphyrin IX fluorescence kinetics and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay showed that ALA PLGA NPs were more effective than free ALA of the same concentration. Conclusion: PLGA NPs provide a promising ALA delivery strategy for topical ALAphotodynamic therapy of skin squamous cell carcinoma.

Tunable phosphatase-sensitive stable prodrugs of 5-aminolevulinic acid for tumor fluorescence photodetection

“…The major reasoning is that increased lipophilicity potentially improves the passage through biological membranes thus increasing intracellular substrate concentration for heme biosynthesis. Recently, substantial efforts have also been directed towards nanocarriers loaded [20][21][22][23][24] or conjugated [25][26][27][28] with 5-ALA. These approaches tackle some of the pharmacokinetic and specificity drawbacks of 5-ALA but have so far failed to produce a clinical candidate for the improved delivery of 5-ALA mostly due to high 5-ALA loading and delivery required for this type of FPD or PDT.…”

Evaluation of polymeric PLGA nanoparticles conjugated to curcumin for use in aPDT

“…Several studies have reported that the encapsulation of photosensitizers in polymeric nanoparticles of poly(lactic-co-glycolic) acid (PLGA) increases the efficiency of photosensitizers in reducing the viability of cancer cells. PLGA is a biomaterial, biodegradable with good biocompatibility and stability, developed in the 1970s and approved by the United States Food and Drug Administration (FDA) for drug delivery (Shi et al, 2013). Ricci-Junior and Marchetti (2006) demonstrated that zinc phthalocyanine is more efficient in reducing the viability of lymphoid lineage P388D1 neoplastic cells.…”

Treating cutaneous squamous cell carcinoma using 5-aminolevulinic acid polylactic-co-glycolic acid nanoparticle-mediated photodynamic therapy in a mouse model

“…7 Our in vitro study suggested that the use of polylactic-co-glycolic acid (PLGA) NPs could improve ALA delivery in human cutaneous SCC cells. 8 The aim of this in vivo study was to evaluate the feasibility of ALA PLGA NP-mediated PDT for the treatment of cutaneous SCC in a mouse model.…”

“…8 The examination of in situ PpIX-fluorescence kinetics showed that SCCs incubated with ALA PLGA NPs generated higher levels of PpIX than those incubated with free ALA of the same concentration ( Figure 2). This is possibly because free ALA might be directly dissolved in the extracellular compartment and decompose, whereas PLGA NPs could protect ALA from such degradation.…”

“…This is possibly because free ALA might be directly dissolved in the extracellular compartment and decompose, whereas PLGA NPs could protect ALA from such degradation. 8 Fluorescence images showed that the PpIX production and accumulation of the ALA PLGA NP group were stronger, more confined to the tumor site, and had weaker fluorescence intensity of surrounding tumor, compared to the ALA group ( Figures 2 and 3). The low tissue penetrability of free ALA might limit its application for deep cancers.…”