ABSTRACT
The zeolitic imidazolate framework ZIF-8 (Zn(mim)2, mim = 2-methylimidazolate) has recently been proposed as a drug delivery platform for anticancer therapy based on its capability of decomposing in acidic media. The concept presumes a targeted release of encapsulated drug molecules in the vicinity of tumor tissues that typically produce secretions with elevated acidity. Due to challenges of in vivo and in vitro examination, many studies have addressed the kinetics of ZIF-8 decomposition and subsequent drug release in phosphate buffered saline (PBS) with adjusted acidity. However, the presence of hydrogen phosphate anions [HPO4]2- in PBS may also affect the stability of ZIF-8. As yet, no separate analysis has been performed comparing the dissolving capabilities of PBS and various acidification agents used for regulating pH. Here, we provide a systematic study addressing the effects of phosphate anions with and without lactic acid on the degradation rate of ZIF-8 microcrystals. Lactic acid has been chosen as an experimental acidification agent, since it is particularly secreted by tumor cells. Interestingly, the effect of a lactic acid solution with pH 5.0 on ZIF-8 degradation is shown to be weaker compared to a PBS solution with pH 7.4. However, as an additive, lactic acid is able to enhance the decomposition efficacy of other solutions by 10 to 40 percent at the initial stage, depending on the presence of other ions. Additionally, we report mild toxicity of ZIF-8 and its decomposition products, as examined on HDF and A549 cell lines.
ABSTRACT
BACKGROUND: Laser procedures for acne and acne scars have traditionally been postponed for at least 6 to 8 months after the end of systemic isotretinoin therapy. Lower dosages with more modern laser devices having unique energy parameters of high power in microsecond pulse durations have made it possible to administer laser therapy during or shortly after completion of isotretinoin therapy, thus reducing the risk of side effects of isotretinoin. METHODS: Patients with moderate to severe facial acne (n=46) and atrophic scars enrolled in a 6-month study. Genetic analysis of patients revealed the presence of polymorphisms of genes Col1A2, MMP3, ESR1, MMP1, and MMP7, which can lead to scar formation. Patients underwent low-dosage isotretinoin therapy (0.2-0.3 mg/kg/day) in combination with facial laser treatment using a 650-microsecond, 1064-nm Nd: YAG laser. Acne severity was graded using the Investigators Global Assessment (IGA) scale and quality of life was evaluated by the Dermatology Life Quality Index (DLQI). RESULTS: IGA parameters decreased from 1.8 ± 0.2 (mean ± SD) initially to 0.5 ± 0.4 at the end of the study, a 72.3% reduction which was significant (P<0.01). The DLQI index decreased from 10.1 ± 1.3 initially to 2.8 ± 1.2, a 72.3%, a significant reduction (P<0.01). Inflammatory elements resolved without scarring. Laser treatment was well tolerated and improvement in pre-existing scars was noticeable. CONCLUSIONS: The 650-microsecond, 1064-nm laser in combination with low-dose isotretinoin is safe and effective in patients with acne complicated by atrophic scars and genetically prone to post-acne scarring. J Drugs Dermatol. 2020;19(6): doi:10.36849/JDD.2020.5108.
