scholarly journals Hyaluronic Acid-Based Gold Nanoparticles for the Topical Delivery of Therapeutics to the Retina and the Retinal Pigment Epithelium

Polymers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 3324
Author(s):  
Amine Laradji ◽  
Bedia Karakocak ◽  
Alexander Kolesnikov ◽  
Vladimir Kefalov ◽  
Nathan Ravi

The ocular immune privilege is a phenomenon brought about by anatomical and physiological barriers to shield the eye from immune and inflammation responses. While this phenomenon is beneficial for eyes protection, it is, at the same time, a hindrance for drug delivery to the posterior segment of the eye to treat retinal diseases. Some ocular barriers can be bypassed by intravitreal injections, but these are associated with several side effects and patient noncompliance, especially when frequent injections are required. As an alternative, applying drugs as an eye drop is preferred due to the safety and ease. This study investigated the possible use of topically-applied hyaluronic acid-coated gold nanoparticles as drug delivery vehicles to the back of the eye. The coated gold nanoparticles were topically applied to mouse eyes, and results were compared to topically applied uncoated gold nanoparticles and phosphate-buffered saline (PBS) solution. Retina sections from these mice were then analyzed using fluorescence microscopy, inductively coupled plasma mass spectrometry (ICP-MS), and transmission electron microscopy (TEM). All characterization techniques used in this study suggest that hyaluronic acid-coated gold nanoparticles have higher distribution in the posterior segment of the eye than uncoated gold nanoparticles. Electroretinogram (ERG) analysis revealed that the visual function of mice receiving the coated gold nanoparticles was not affected, and these nanoparticles can, therefore, be applied safely. Together, our results suggest that hyaluronic acid-coated gold nanoparticles constitute potential drug delivery vehicles to the retina when applied noninvasively as an eye drop.

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1407
Author(s):  
Courtney van Ballegooie ◽  
Alice Man ◽  
Alessia Pallaoro ◽  
Marcel Bally ◽  
Byron D. Gates ◽  
...  

Drug-delivery vehicles have been used extensively to modulate the biodistribution of drugs for the purpose of maximizing their therapeutic effects while minimizing systemic toxicity. The release characteristics of the vehicle must be balanced with its encapsulation properties to achieve optimal delivery of the drug. An alternative approach is to design a delivery vehicle that preferentially releases its contents under specific endogenous (e.g., tissue pH) or exogenous (e.g., applied temperature) stimuli. In the present manuscript, we report on a novel delivery system with potential for triggered release using external beam radiation. Our group evaluated Zein protein as the basis for the delivery vehicle and used radiation as the exogenous stimulus. Proteins are known to react with free radicals, produced during irradiation in aqueous suspensions, leading to aggregation, fragmentation, amino acid modification, and proteolytic susceptibility. Additionally, we incorporated gold particles into the Zein protein matrix to create hybrid Zein–gold nanoparticles (ZAuNPs). Zein-only nanoparticles (ZNPs) and ZAuNPs were subsequently exposed to kVp radiation (single dose ranging from 2 to 80 Gy; fractionated doses of 2 Gy delivered 10 times) and characterized before and after irradiation. Our data indicated that the presence of gold particles within Zein particles was correlated with significantly higher levels of alterations to the protein, and was associated with higher rates of release of the encapsulated drug compound, Irinotecan. The aggregate results demonstrated a proof-of-principle that radiation can be used with gold nanoparticles to modulate the release rates of protein-based drug-delivery vehicles, such as ZNPs.


2014 ◽  
Vol 2 (27) ◽  
pp. 4204-4220 ◽  
Author(s):  
I. Fratoddi ◽  
I. Venditti ◽  
C. Cametti ◽  
M. V. Russo

Gold nanoparticles and their conjugates as drug delivery vehicles for selective targeting of cancer cells.


2021 ◽  
Author(s):  
Adedoja Dorcas Wusu ◽  
Nicole Remaliah Samantha Sibuyi ◽  
Koena Leah Moabelo ◽  
Mediline Goboza ◽  
Abram Madiehe ◽  
...  

Abstract Advancements in nanotechnology have provided insight into the unique opportunities for the application of nanomaterials such as gold nanoparticles (AuNPs) in medicine due to their remarkable properties, which includes low toxicity, large surface area, and the ease of synthesis and conjugation to other molecules. Therefore, AuNPs are often preferred for bio-applications. Citrate-capped AuNPs (cAuNPs) have been reported to be non-cytotoxic and are used in numerous studies as drug delivery vehicles to treat various diseases. However, the limitations of bioassays often used to assess the toxicity of AuNPs have been well documented. Herein, we investigate the cytotoxicity of 14nm cAuNPs in the human colorectal adenocarcinoma (Caco-2) cell line. Treatment conditions (i.e., dose and exposure time) that were established to be non-toxic to Caco-2 cells were used to investigate the effect of cAuNPs on the expression of a Qiagen panel of 86 genes involved in cytotoxicity. Out of 86 studied, 23 genes were differentially expressed. Genes involved in oxidative stress and antioxidant response, endoplasmic reticulum (ER) stress and unfolded protein response (UPR), heat shock response (HSR), and lipid metabolism were more affected than others. While low concentrations of 14nm cAuNPs was not cytotoxic and did not cause cell death, cells treated with these nanoparticles experienced ER and oxidative stress, resulting in the activation of cytoprotective cellular processes. Additionally, several genes involved in lipid metabolism were also affected. Therefore, 14nm cAuNPs can safely be used as drug delivery vehicles at low doses.


2020 ◽  
Vol 850 ◽  
pp. 213-218
Author(s):  
Elīza Tračuma ◽  
Dagnija Loca

Site specific drug delivery systems (DDS) are usually developed to overcome the side effects of conventional ones (e.g. injections or oral ingestions), creating smart drug delivery vehicles characterized with greater efficiency, safety, predictable therapeutic response as well as controlled and prolonged drug release periods. DDS made of hyaluronic acid (HA) and poly-L-lysine (PLL) are promising candidates in the field of local drug delivery due to their high biocompatibility. Moreover, electrostatic attractions between negatively charged HA and positively charged PLL can be used to fabricate multilayer films, bilayer films and hydrogels, avoiding the application of toxic crosslinking agents. In this review, we report the preparation of HA/PLL composites exploiting their intrinsic properties, as well as developed composite application possibilities as controlled drug delivery systems in bone tissue, central nervous system and gene engineering.


2017 ◽  
Vol 18 (1) ◽  
pp. 1700200 ◽  
Author(s):  
Tina Borke ◽  
Mathie Najberg ◽  
Polina Ilina ◽  
Madhushree Bhattacharya ◽  
Arto Urtti ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document