Page 91 - CSIR-IGIB Annual Report 2020-21
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Glycosaminoglycans like hyaluronic acid and chondroitin sulphate and exhibit protection of
chondroitin sulphate play major roles in skin mouse skin from UV-B radiation. This could be
physiology. Their replenishment in skin developed as an effective formulation for
becomes necessary because of the loss of these photoprotection from UV irradiation.
molecules due to ageing or under disease
conditions. However, the skin with its complex A mucus penetrating nucleic acid delivery
structure of lipids, proteins and embedded system
corneocytes can pose a challenging barrier for
such high molecular weight and hydrophilic Nucleic acids are potential therapeutics for
molecules to penetrate the barrier. Such treatment of various lung disorders. However,
molecules are unable to diffuse effectively delivery of nucleic acids to lungs can be quite
through the skin and therefore need challenging due to the barrier property imposed
appropriate carriers for their transport. Most of by mucus which is further reinforced in diseased
the known physical and chemical methods of conditions. The mesh network structure of
topical delivery to the skin are abrasive in mucus can create steric hindrance for the entry
nature. We have developed a method of of the delivery system and the negatively
delivery of chondroitin sulphate as charged mucins can impart an electrostatic
nanocomplexes to skin in a topical and non- barrier. For effective penetration, the delivery
invasive manner. We have shown the anti- system needs to either have the ability to
inflammatory and antioxidant property of transiently dismantle mucus structure and
chondroitin sulphate in these nanocomplexes rheology or be mucoinert with low positive
using UV irradiation as a model condition. The charge so as to reduce interactions with the
nanocomplexes were prepared through mucus. We have developed a plasmid DNA and
electrostatic assembly of chondroitin sulphate siRNA delivery system which has the ability of
with an arginine-rich skin penetrating peptide mucus penetration. The nanocomplex delivery
developed in our laboratory and were stable at system is made of nucleic acid (pDNA/siRNA)
physiological conditions. They were efficiently condensed using a cationic/amphipathic
delivered to skin keratinocytes, to mouse tissue peptide developed in our laboratory. This is
ex vivo where localization was restricted to the coated with a hydrophilic biopolymer
epidermis and to model membrane mimicking chondroitin sulphate A (CS-A) conjugated with a
human skin where no transdermal penetration mucolytic agent mannitol-a known molecule for
was observed indicating localization in skin reducing the viscosity of mucus by increasing
layers. In addition, we could demonstrate the the influx of water. The presence of the
efficiency of these nanocomplexes in protecting hydrophilic coating of CS-A reduces the surface
the skin from UV-B irradiation by analyzing the positive charge, thus reducing the interaction
cellular and tissue effects in vitro and in vivo. with the negatively charged mucins and the
The pre-application of nanocomplexes conjugated mannitol increases the diffusion of
exhibited reduced levels of oxidative stress, nanocomplexes in mucus by possibly through
cyclobutane pyrimidine dimer formation and the osmotically active property. The
TNF-a levels in UV-B irradiated HaCaT cells. In nanocomplexes also show high cellular uptake
acute UV-B irradiation mouse model, their and transfection in A549 and BEAS2B cells and
topical application reduced the epidermal show very low cytotoxicity. Subsequently, we
thickness and amount of sunburn cells. Our have tried to utilize the best mucus penetration
results indicate that chondroitin sulphate, when system developed in our laboratory to deliver
topically delivered as nanocomplexes to skin, antifibrotic miRNAs to prevent quartz induced
have negligible toxic effects on keratinocytes, fibrosis of the lung. A quartz-induced fibrosis
show effective skin penetration and localization model has been developed in the laboratory for
in the epidermis in mouse skin unlike free this purpose and conditions for in vivo delivery
Annual Report 2020-21 88
