Targeted delivery of hyaluronic acid to the ocular surface by a polymer-peptide conjugate system for dry eye disease

Lee, David; Lu, Qiaozhi; Sommerfeld, Sven D.; Chan, Amanda; Menon, Nikhil G.; Schmidt, Tannin A.; Elisseeff, Jennifer H.; Singh, Anirudha

doi:10.1016/j.actbio.2017.03.043

Cited by 39 publications

(17 citation statements)

References 54 publications

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“…The use of HA has been implicated in various ophthalmic conditions, including keratoconjuctivitis sicca (KCS) or dry eye disease (DED) in humans and animals (9, 10, 288–293). HA solutions (0.1% HA) effectively lubricate the ocular surface and are used for the relief of dry eye related symptoms (294). However, HA undergoes rapid clearance due to limited adhesion, which necessitates frequent instillation.…”

Section: Pharmacotherapeutics Of Hamentioning

confidence: 99%

“…Furthermore, highly viscous artificial tear formulations with HA blur vision and interfere with blinking. Lee et al (294) synthesized a heterobifunctional polymer-peptide system with one end binding HA while the other end binds either sialic acid-containing glycosylated transmembrane molecules on the ocular surface epithelium, or type I collagen molecule within the tissue matrix. These investigators treated rabbit ocular surface tissues with binding peptides and HA solutions and demonstrated superior lubricating with long-lasting effect, and reduced kinetic friction coefficients compared to tissues treated with conventional HA solution.…”

Section: Pharmacotherapeutics Of Hamentioning

confidence: 99%

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Hyaluronic Acid: Molecular Mechanisms and Therapeutic Trajectory

Gupta

Lall²,

Srivastava³

et al. 2019

Front. Vet. Sci.

521

345

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Hyaluronic acid (also known as hyaluronan or hyaluronate) is naturally found in many tissues and fluids, but more abundantly in articular cartilage and synovial fluid (SF). Hyaluronic acid (HA) content varies widely in different joints and species. HA is a non-sulfated, naturally occurring non-protein glycosaminoglycan (GAG), with distinct physico-chemical properties, produced by synoviocytes, fibroblasts, and chondrocytes. HA has an important role in the biomechanics of normal SF, where it is partially responsible for lubrication and viscoelasticity of the SF. The concentration of HA and its molecular weight (MW) decline as osteoarthritis (OA) progresses with aging. For that reason, HA has been used for more than four decades in the treatment of OA in dogs, horses and humans. HA produces anti-arthritic effects via multiple mechanisms involving receptors, enzymes and other metabolic pathways. HA is also used in the treatment of ophthalmic, dermal, burns, wound repair, and other health conditions. The MW of HA appears to play a critical role in the formulation of the products used in the treatment of diseases. This review provides a mechanism-based rationale for the use of HA in some disease conditions with special reference to OA.

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Section: Pharmacotherapeutics Of Hamentioning

confidence: 99%

Section: Pharmacotherapeutics Of Hamentioning

confidence: 99%

Hyaluronic Acid: Molecular Mechanisms and Therapeutic Trajectory

Gupta

Lall²,

Srivastava³

et al. 2019

Front. Vet. Sci.

521

345

View full text Add to dashboard Cite

show abstract

“…As a result, Lee et al developed HA-loaded polymer-peptide conjugated eye drops. The study showed sustained delivery of the HA for a prolonged period of time in both ex vivo and in vivo conditions, and may provide an alternative therapy for dry eye syndrome [ 163 ]. There is some evidence to suggest that HA may help in the acceleration of wound healing [ 164 ].…”

Section: Polysaccharidesmentioning

confidence: 99%

Smart Carriers and Nanohealers: A Nanomedical Insight on Natural Polymers

et al. 2017

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Biodegradable polymers are popularly being used in an increasing number of fields in the past few decades. The popularity and favorability of these materials are due to their remarkable properties, enabling a wide range of applications and market requirements to be met. Polymer biodegradable systems are a promising arena of research for targeted and site-specific controlled drug delivery, for developing artificial limbs, 3D porous scaffolds for cellular regeneration or tissue engineering and biosensing applications. Several natural polymers have been identified, blended, functionalized and applied for designing nanoscaffolds and drug carriers as a prerequisite for enumerable bionano technological applications. Apart from these, natural polymers have been well studied and are widely used in material science and industrial fields. The present review explains the prominent features of commonly used natural polymers (polysaccharides and proteins) in various nanomedical applications and reveals the current status of the polymer research in bionanotechnology and science sectors.

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“…The main reason for this problem is that ocular protective mechanisms (involving blinking, both basal and reflex lachrymation, and a drainage through nasolacrimal ducts) quickly eliminates these eye drops from the precorneal region, where such drugs are absorbed and work [ 1 ]. As a result, and depending on the severity, this can lead to the need for repeated administration [ 2 ]. Therefore, various studies have investigated novel preparations to overcome such disadvantages of currently available formulations.…”

Section: Introductionmentioning

confidence: 99%

“…Of the two components, both natural polysaccharides, HA is a linear polyanionic molecule chemically grouped in a glycosaminoglycan and comprises the repeating dimer {

4)-

-D-glucopyranosyluronic acid-(1

3)- N -acetyl-2-amino-2-deoxy-

- d -glycopyranosyl-(1

} [ 7 , 8 ]. When it comes to the current market situation, it has been reported [ 2 ] that 0.1–0.5% ( w/v ) HA solutions are available commercially as either active or inactive ingredients to supplement ocular fluid (see also refs [ 9 ] and [ 10 ]). Hammer and Burch [ 11 ] have suggested that 0.17% HA showed superior protective effects as a coating on the eye compared to the highly viscous, more concentrated applications (1%, equivalent to 10 mg/mL) which transmit excessive shear force to endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

Hydrodynamic Compatibility of Hyaluronic Acid and Tamarind Seed Polysaccharide as Ocular Mucin Supplements

et al. 2020

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Hyaluronic acid (HA) has been commonly used in eyedrop formulations due to its viscous lubricating properties even at low concentration, acting as a supplement for ocular mucin (principally MUC5AC) which diminishes with aging in a condition known as Keratoconjunctivitis sicca or “dry eye”. A difficulty has been its short residence time on ocular surfaces due to ocular clearance mechanisms which remove the polysaccharide almost immediately. To prolong its retention time, tamarind seed gum polysaccharide (TSP) is mixed as a helper biopolymer with HA. Here we look at the hydrodynamic characteristics of HA and TSP (weight average molar mass Mw and viscosity ) and then explore the compatibility of these polymers, including the possibility of potentially harmful aggregation effects. The research is based on a novel combination of three methods: sedimentation velocity in the analytical ultracentrifuge (SV-AUC), size-exclusion chromatography coupled to multiangle light scattering (SEC-MALS) and capillary viscometry. HA and TSP were found to have ) kg/mol and ) kg/mol respectively, and and ml/g, respectively. The structure of HA ranges from a rodlike molecule at lower molar masses changing to a random coil for Mw > 800 kg/mol, based on the Mark–Houwink–Kuhn–Sakurada (MHKS) coefficient. TSP, by contrast, is a random coil across the range of molar masses. For the mixed HA-TSP systems, SEC-MALS indicates a weak interaction. However, sedimentation coefficient (s) distributions obtained from SV-AUC measurements together with intrinsic viscosity demonstrated no evidence of any significant aggregation phenomenon, reassuring in terms of eye-drop formulation technology involving these substances.

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Targeted delivery of hyaluronic acid to the ocular surface by a polymer-peptide conjugate system for dry eye disease

Cited by 39 publications

References 54 publications

Hyaluronic Acid: Molecular Mechanisms and Therapeutic Trajectory

Hyaluronic Acid: Molecular Mechanisms and Therapeutic Trajectory

Smart Carriers and Nanohealers: A Nanomedical Insight on Natural Polymers

Hydrodynamic Compatibility of Hyaluronic Acid and Tamarind Seed Polysaccharide as Ocular Mucin Supplements

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