Fiber Optic Microneedles for Transdermal Light Delivery: Ex Vivo Porcine Skin Penetration Experiments

2010 ◽  
Vol 132 (9) ◽  
Author(s):  
Mehmet A. Kosoglu ◽  
Robert L. Hood ◽  
Ye Chen ◽  
Yong Xu ◽  
Marissa Nichole Rylander ◽  
...  

Shallow light penetration in tissue has been a technical barrier to the development of light-based methods for in vivo diagnosis and treatment of epithelial carcinomas. This problem can potentially be solved by utilizing minimally invasive probes to deliver light directly to target areas. To develop this solution, fiber optic microneedles capable of delivering light for either imaging or therapy were manufactured by tapering step-index silica-based optical fibers employing a melt-drawing process. Some of the microneedles were manufactured to have sharper tips by changing the heat source during the melt-drawing process. All of the microneedles were individually inserted into ex vivo pig skin samples to demonstrate the feasibility of their application in human tissues. The force on each microneedle was measured during insertion in order to determine the effects of sharper tips on the peak force and the steadiness of the increase in force. Skin penetration experiments showed that sharp fiber optic microneedles that are 3 mm long penetrate through 2 mm of ex vivo pig skin specimens. These sharp microneedles had a minimum average diameter of 73 μm and a maximum tip diameter of 8 μm. Flat microneedles, which had larger tip diameters, required a minimum average diameter of 125 μm in order to penetrate through pig skin samples. Force versus displacement plots showed that a sharp tip on a fiber optic microneedle decreased the skin’s resistance during insertion. Also, the force acting on a sharp microneedle increased more steadily compared with a microneedle with a flat tip. However, many of the sharp microneedles sustained damage during skin penetration. Two designs that did not accrue damage were identified and will provide a basis of more robust microneedles. Developing resilient microneedles with smaller diameters will lead to transformative, novel modes of transdermal imaging and treatment that are less invasive and less painful for the patient.

Theranostics ◽  
2017 ◽  
Vol 7 (14) ◽  
pp. 3517-3526 ◽  
Author(s):  
Kan Lin ◽  
Wei Zheng ◽  
Chwee Ming Lim ◽  
Zhiwei Huang

2020 ◽  
Vol 10 (7) ◽  
pp. 2281
Author(s):  
Santiago Camacho-Lopez ◽  
Carlos Andrés Zuñiga-Romero ◽  
Luis Felipe Devia-Cruz ◽  
Carolina Alvarez-Delgado ◽  
Marcos Antonio Plata-Sanchez ◽  
...  

Traditional applanation tonometry techniques lack the necessary accuracy and reliability for measuring the intraocular pressure (IOP), and there is still a need for a reliable technique for in vivo diagnosis. A single laser-induced cavitation bubble event was optically monitored in order to precisely measure the first collapse time of the cavitation bubble, which presents a direct dependence on the liquid pressure. This can certainly be done within the IOP range. We now extend the partial transmittance modulation (STM) technique to determine its feasibility for directly measuring the IOP by studying the nanosecond (ns) pulsed laser-induced cavitation bubble dynamics for an externally pressurized fresh ex vivo porcine eye. The results demonstrate that it is possible to monitor the IOP by detecting the light of a continuous-wave (CW) laser beam which is intensity modulated by the bubble itself. This technique currently presents a measurement resolution of about 4 mmHg in the 5 to 50 mmHg pressure range, indicating the feasibility of this approach for measuring IOP. This technique provides a direct measurement within the anterior eye chamber, avoiding common pitfalls in IOP diagnosis, such as errors due to patient movement, varying physical properties of the eye globe, or central cornea thickness (CCT) effects.


Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 310 ◽  
Author(s):  
Stella Zsikó ◽  
Kendra Cutcher ◽  
Anita Kovács ◽  
Mária Budai-Szűcs ◽  
Attila Gácsi ◽  
...  

The aim of this research was to investigate the stability of a lidocaine-loaded nanostructured lipid carrier dispersion at different temperatures, formulate a nanostructured lipid carrier gel, and test the penetration profile of lidocaine from the nanostructured lipid carrier gel using different skin penetration modeling methods. The formulations were characterized by laser diffraction, rheological measurements and microscopic examinations. Various in vitro methods were used to study drug release, diffusion and penetration. Two types of vertical Franz diffusion cells with three different membranes, including cellulose, Strat-M®, and heat separated human epidermis were used and compared to the Skin-parallel artificial membrane permeability assay (PAMPA) method. Results indicated that the nanostructured lipid carrier dispersion had to be gelified as soon as possible for proper stability. Both the Skin-PAMPA model and Strat-M® membranes correlated favorably with heat separated human epidermis in this research, with the Strat-M® membranes sharing the most similar drug permeability profile to an ex vivo human skin model. Our experimental findings suggest that even when the best available in vitro experiment is selected for modeling human skin penetration to study nanostructured lipid carrier gel systems, relevant in vitro/in vivo correlation should be made to calculate the drug release/permeation in vivo. Future investigations in this field are still needed to demonstrate the influence of membranes and equipment from other classes on other drug candidates.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 814
Author(s):  
Momoko Kitaoka ◽  
Atsushi Oka ◽  
Masahiro Goto

An increasing number of protein vaccines have been researched for cancer, inflammation, and allergy therapies. Most of the protein therapeutics are administered through injection because orally-administered proteins are metabolized by the digestive system. Although transdermal administration has received increasing attention, the natural barrier formed by the skin is an obstacle. Monoolein is a common skin penetration enhancer that facilitates topical and transdermal drug delivery. Conventionally, it has been used in an aqueous vehicle, often with polyhydric alcohols. In the current study, monoolein was dissolved in an oil vehicle, isopropyl myristate, to facilitate the skin permeation of powder proteins. The skin permeabilities of the proteins were examined in-vivo and ex-vivo. Monoolein concentration-dependently enhanced the skin permeation of proteins. The protein permeability correlated with the zeta potential of the macromolecules. Dehydration of the stratum corneum (SC), lipid extraction from the SC, and disordering of ceramides caused by monoolein were demonstrated through Fourier transform infrared spectroscopic analysis and small-angle X-ray scattering analysis. An antigen model protein, ovalbumin from egg white, was delivered to immune cells in living mice, and induced antigen-specific IgG antibodies. The patch system showed the potential for transdermal vaccine delivery.


2016 ◽  
Author(s):  
Kan Lin ◽  
Wei Zheng ◽  
Jianfeng Wang ◽  
Chwee Ming Lim ◽  
Zhiwei Huang

2020 ◽  
Vol 10 (24) ◽  
pp. 8836
Author(s):  
Pankaj Singh ◽  
Prabodh Pandey ◽  
Shivam Shukla ◽  
Naren Naik ◽  
Asima Pradhan

Fiber-optic probes are imperative for in-vivo diagnosis of cancer. Depending on the access to a diseased organ and the mutations one aims to sense, the probe designs vary. We carry out a detailed numerical study of the efficacy of the common probe geometries for epithelial cancer characterization based on spatially resolved reflectance data. As per the outcomes of this comparative study, a probe has been manufactured and using Monte Carlo look up table based inversion scheme, the absorption and scattering coefficients of the epithelium mimicking top layer have been recovered from noisy synthetic as well as experimental data.


2016 ◽  
Vol 7 (9) ◽  
pp. 3705 ◽  
Author(s):  
Kan Lin ◽  
Wei Zheng ◽  
Chwee Ming Lim ◽  
Zhiwei Huang

2002 ◽  
Vol 118 (3) ◽  
pp. 540-544 ◽  
Author(s):  
Heike Wagner ◽  
Claus-Michael Lehr ◽  
Ulrich F. Schaefer ◽  
Karl-Heinz Kostka

Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 67
Author(s):  
Richard Krombholz ◽  
Yali Liu ◽  
Dominique Jasmin Lunter

Ex-vivo and in-vivo skin analysis has been extensively evaluated by confocal Raman spectroscopy (CRS). The off-line measurement with a CRS-suited skin-mounted device after Franz-cell incubations is the most popular choice. However, real-time monitoring of in-line measurement has clear advantages for obtaining dynamic and more timely results. In our study, a custom-built setup suitable for in-line measurements was implemented, which ensures constant skin incubation and in-situ skin detections. We aim to compare the differences between using in-line and off-line devices for monitoring skin drug penetrations. A well-assessed formulation gel with procaine-HCl as the active ingredient was used as reference. The PEG-23 lauryl ether was added to the formulation as a penetration enhancer to evaluate the enhancement effects of procaine on skin. After incubation times of 14, 20, and 24 h, skin penetration profiles were assessed. Comparable results between off-line and in-line measurements were obtained. Remarkable improvements in penetrated procaine amount and depth were observed. Based on the significant differences of their enhanced penetration amounts, fairly similar estimations were achieved from both methods. A slight difference of 14 h incubation between these two setups can still be found, which may be due to the different detection conditions and affected skin properties. Overall, in-line measurements could provide a more time- and labor-saving alternative for off-line measurements in ex-vivo study.


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