Worranan Rangsimawong

Skin Transport of Hydrophilic Compound-Loaded PEGylated Lipid Nanocarriers: Comparative Study of Liposomes, Niosomes, and Solid Lipid Nanoparticles

The effect of surface grafting with N-(carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (PEG2000-DSPE) onto three types of lipid nanocarriers, liposomes, niosomes and solid lipid nanoparticles (SLNs) on the skin penetration of sodium fluorescein (NaFI) was investigated. Confocal laser scanning microscopy (CLSM) was used to visualize the penetration pathways. Fourier transform infrared spectroscopy (FT-IR) was used to determine the skin hydration. The results showed that the physicochemical properties of each nanocarrier were modified after PEG grafting. In the skin penetration study, PEG grafting increased the flux of NaFI-loaded PEGylated liposomes and significantly decreased the flux of NaFI-loaded PEGylated niosomes and NaFI-loaded PEGylated SLNs. The skin deposition study and CLSM images showed that the intact liposome vesicles permeated into the skin. The niosomes and SLNs had little or no vesicles in the skin, suggesting that NaFI may have been released from these nanocarriers before permeation. Additionally, the fluorescent CLSM images of the SLNs showed that NaFI deposited along the length of hair follicles inside the skin, indicating that the skin penetration route may be through the transfollicular pathway. For the PEGylated nanocarriers, the PEGylated liposomes had higher fluorescence intensities than the non-PEGylated liposomes, indicating higher NaFI concentrations. The PEGylated niosomes and PEGylated SLNs had lower fluorescence intensities than those of the non-PEG modified niosomes and SLNs. For FT-IR results, PEGylated liposomes increased the skin hydration, while the grafting PEG onto niosomes and SLN surfaces decreased the skin hydration. This study showed that the surface grafting of PEG onto various nanocarriers affected the skin transport of NaFI.

Mechanistic study of decreased skin penetration using a combination of sonophoresis with sodium fluorescein-loaded PEGylated liposomes with D-limonene

The effect of low frequency sonophoresis (SN, 20 kHz) on the skin transport of sodium fluorescein (NaFI)-loaded liposomes was investigated. An in vitro skin penetration study in open and blocked hair follicles was performed, and confocal laser scanning microscopy and scanning electron microscopy were used to visualize the penetration pathways. The results showed that SN significantly increased the flux of NaFI solution, whereas it significantly decreased the flux of NaFI-loaded polyethylene glycol-coated (PEGylated) liposomes with D-limonene (PL-LI). SN did not significantly affect the flux of NaFI-loaded conventional liposomes and PEGylated liposomes. In the blocked follicles, the flux of NaFI-loaded PL-LI both with and without SN decreased, indicating that NaFI-loaded PL-LI penetrated the skin via the transfollicular pathway. A confocal laser scanning microscopy image showed that in the skin without SN, the fluorescence intensity of NaFI-loaded PL-LI was observed in the skin and along the length of hair inside the skin, whereas in the skin with applied SN, the fluorescence intensity was detected only on the top of hair outside the skin. From scanning electron microscopy images, SN dislocated the corneocytes and reduced the deposition of PL-LI around hair follicles. These results revealed that SN may partially plug hair follicle orifices and reduce percutaneous absorption through the follicular pathway.

Influence of sonophoresis on transdermal drug delivery of hydrophilic compound-loaded lipid nanocarriers

Abstract The effect of sonophoresis on the transdermal drug delivery of sodium fluorescein (NaFI)-loaded lipid nanocarriers such as liposomes (LI), niosomes (NI) and solid lipid nanoparticles (SLN) was investigated by confocal laser scanning microscopy (CLSM), fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The results showed that SN decreased the skin penetration of NaFI-loaded SLN (6.32-fold) and NI (1.79-fold), while it increased the penetration of NaFI-loaded LI (5.36-fold). CLSM images showed the red fluorescence of the LI and NI bilayer on the superficial layer of the stratum corneum. However, the red fluorescent probe of the SLN was not visualized in the skin. FTIR results of the LI and NI with SN showed no effect on lipid stratum corneum ordering, suggesting that the fragment of bilayer vesicles might repair the damaged skin. For SLN, the strengthening of stratum corneum by covering the disrupted skin with solid lipids was shown. SEM images show disrupted carriers of all the formulations adsorbed onto the damaged skin. In conclusion, the SN changed the properties of both the skin surface and lipid nanocarrier, demonstrating that disrupted skin might be repaired by a disrupted nanocarrier.

Chitosan-based self-assembled nanocarriers coordinated to cisplatin for cancer treatment

Polymeric nanocarriers were prepared via a dialysis method using three chitosan derivatives, N-benzyl-N,O-succinyl chitosan (BSCT), N-naphthyl-N,O-succinyl chitosan (NSCT), and N-octyl-N-O-succinyl chitosan (OSCT) and were coordinated to cisplatin. The nanocarrier properties and cytotoxicity on the human carcinoma cells, HN22 (head and neck), were investigated. In addition, intracellular cisplatin accumulation, apoptosis induction and toxicity on renal cells were also evaluated. The findings revealed that the succinyl groups of the polymers were perfectly deprotonated and bound with cisplatin by co-ordinate bonds at pH 8.5. Among the derivatives, BSCT exhibited the highest cisplatin loading and release in simulated physiological medium. The cytotoxicities on HN22 cells of cisplatin-loaded BSCT nanocarriers were lower than that of free cisplatin, however, they presented a greater percentage of early apoptosis in HN22 cells and could decrease cisplatin induced renal cell death. In conclusion, the BSCT self-assembly nanocarrier might be a cisplatin carrier for sustained release, which provides prolonged antitumour treatment and reduced nephrotoxicity.

Development of Microemulsions and Microemulgels for Enhancing Transdermal Delivery of Kaempferia parviflora Extract

The purpose of this research was to develop microemulsions (ME) and microemulgels (MG) for enhancing transdermal delivery of Kaempferia parviflora (KP) extract. The methoxyflavones were used as markers. Various formulations of ME and MG containing 10% w/v KP extract were prepared, and the in vitro skin permeation and deposition were investigated. The potential ME system containing oleic acid (5% w/v), Tween 20 (20% w/v), PG (40% w/v), and water (35% w/v) was successfully formulated. ME with 10% w/v limonene (ME-L10%) showed higher methoxyflavones flux than ME-L5%, ME-L1%, ME without limonene, and KP extract in water, respectively. ME-L10% was selected for adding a gelling agent to form microemulgels (MG-L10%). However, the high viscosity of the gel formulation might control the diffusion of the compound from gel layer into the skin. Therefore, the liquid formulation provided potential ME droplets to deliver KP extract through the skin. Limonene also plays an effective role on the skin permeation, in which the histological image of the skin treated with ME-L10% exhibited larger space of each flattened keratinocyte layer in the stratum corneum compared to the skin treated with KP extract in water. Moreover, ME-L10% showed good stability. Therefore, ME-L10% was a potential formulation for improving transdermal delivery of KP extract.

Enhancement of Galantamine HBr Skin Permeation Using Sonophoresis and Limonene-Containing PEGylated Liposomes

This study aimed to investigate the effect of low-frequency sonophoresis (SN) and limonene-containing PEGylated liposomes (PL) on the transdermal delivery of galantamine HBr (GLT). To evaluate the skin penetration mechanism, confocal laser scanning microscopy (CLSM), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC) were employed. The application of SN led to more GLT penetration into and through the skin than GLT solution alone. The liposomes also improved GLT permeation, and 2% limonene-containing PL (PL-LI2%) exhibited the highest GLT permeation, followed by PL-LI1%, PL-LI0.1%, and PL. The CLSM images of PL-LI2% resulted in the highest fluorescence intensity of fluorescent hydrophilic molecules in the deep skin layer, and the rhodamine PE-labeled liposome membrane was distributed in the intercellular region of the stratum corneum (SC). PL-LI2% induced significant changes in intercellular lipids in the SC, whereas SN had no effect on intercellular lipids of the SC. DSC thermograms showed that the greatest decrease in the lipid transition temperature occurred in PL-LI2%-treated SC. SN might improve drug permeation through an intracellular pathway, while limonene-containing liposomes play an important role in delivering GLT through an intercellular pathway by increasing the fluidity of intercellular lipids in the SC. Moreover, a small vesicle size and high membrane fluidity might enhance the transportation of intact vesicles through the skin.