Hyaluronic acid ester microspheres as a nasal delivery system for insulin

Illum, Lisbeth; Farraj, Nidal F.; Fisher, A. N.; Gill, I. Jabbal; Miglietta, Maria Rosaria; Benedetti, L.

doi:10.1016/0168-3659(94)90129-5

Cited by 90 publications

(33 citation statements)

References 18 publications

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“…HA has been used topically to reduce postoperative pericardial adhesions and as an aerosol to prevent elastase-mediated injury in pulmonary emphysema (57). HA is also used as a vehicle for drug delivery (58). Because of the wide use of HA in medical applications, it is important that we understand the biological effects of HA and how its synthesis and degradation are regulated in humans.…”

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confidence: 99%

Identification of the Hyaluronan Receptor for Endocytosis (HARE)

Zhou

Weigel

Fauss

et al. 2000

Journal of Biological Chemistry

239

222

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Rat liver sinusoidal endothelial cells (LECs) express two hyaluronan (HA) receptors, of 175 and 300 kDa, responsible for the endocytic clearance of HA. We have characterized eight monoclonal antibodies (mAbs) raised against the 175-kDa HA receptor partially purified from rat LECs. These mAbs also cross-react with the 300-kDa HA receptor. The 175-kDa HA receptor is a single protein, whereas the 300-kDa species contains three subunits, ␣, ␤, and ␥ at 260, 230, and 97 kDa, respectively (Zhou, B., Oka, J. A., and Weigel, P. H. (1999) J. Biol. Chem. 274, 33831-33834). The 97-kDa subunit was not recognized by any of the mAbs in Western blots. Based on their cross-reactivity with these mAbs, the 175-, 230-, and 260-kDa proteins appear to be related. Two of the mAbs inhibit 125 I-HA binding and endocytosis by LECs at 37°C. All of these results confirm that the mAbs recognize the bone fide LEC HA receptor. Indirect immunofluoresence shows high protein expression in liver sinusoids, the venous sinuses of the red pulp in spleen, and the medullary sinuses of lymph nodes. Because the tissue distribution for this endocytic HA receptor is not unique to liver, we propose the name HARE (HA receptor for endocytosis). HA1 is an important and often abundant extracellular matrix component of all tissues, in particular cartilage, skin, and vitreous humor (1). HA plays a key role in development, morphogenesis, and differentiation, in cell adhesion and proliferation, and in inflammation and wound healing (1-4). In humans the total body turnover of HA is several grams per day (1). Although local turnover of HA occurs in avascular tissues, particularly cartilage (5, 6), two major clearance systems are responsible for HA degradation and removal in the body (4). The first is the lymphatic system, which accounts for ϳ85% of the HA turnover, and the second is in the liver, which accounts for the other ϳ15% of the total body HA turnover. Throughout the body, HA is continuously synthesized and degraded in almost all tissues. At the same time, chondroitin sulfate and other glycosaminoglycans are also released from the cleavage of proteoglycans, especially aggregating proteoglycans associated with HA. Large native HA molecules (ϳ10 7 Da) are partially degraded to large fragments (ϳ10 6 Da) that are released from the matrix and enter the lymphatic system, flowing to lymph nodes.The lymph nodes completely degrade the majority of HA (ϳ85%) by unknown mechanisms. Neither the responsible cell type, the receptor involved, nor the location in lymph nodes at which HA uptake and degradation occurs has been determined. The remaining HA (ϳ15%) that escapes degradation in the lymph nodes ultimately flows into the blood at the thoracic duct. Since HA is an exceptionally viscous polysaccharide in solution, it would be deleterious for the blood concentration of HA, even at relatively low molecular weight, to increase. Clearance of this circulating HA and the other glycosaminoglycan degradation fragments is presumably important for normal health (1, 4). Elevate...

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confidence: 99%

Identification of the Hyaluronan Receptor for Endocytosis (HARE)

Zhou

Weigel

Fauss

et al. 2000

Journal of Biological Chemistry

239

222

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“…The mucoadhesive properties of HA could enhance the absorption of drugs and proteins via mucosal tissues (Lim et al, 2000;Cho et al, 2003;Ludwig, 2005) as reported in the case where SA solution resulted in enhanced nasal absorption of vasopressin (Morimoto et al, 1991). A study conducted in sheep, HA ester microspheres of insulin for the nasal delivery resulted in a significant increase in drug absorption (Illum et al, 1994). Moreover, a bioadhesive delivery system for the intranasal administration of a flu vaccine which comprised of esterified hyaluronic acid (HYAFF) microspheres in combination with a mucosal adjuvant (LTK63) was also reported to be effective (Singh et al, 2001).…”

Section: Nasal Deliverymentioning

confidence: 99%

“…It also constitutes the backbone of cartilage proteoglycan. Because of its unique physicochemical properties and various biological functions, HA and modified HA have been extensively investigated and widely used for pharmaceutical and medical applications, (Balazs and Denlinger, 1993;Illum et al, 1994;Hahn et al, 2004;Ohri et al, 2004) such as for arthritis treatment (Balazs and Denlinger, 1993), ophthalmic surgery (Bothner and Wik, 1987), drug development , and tissue engineering (West et al, 1985;Ohri et al, 2004). HA is known to be involved in wound healing, promoting cell motility and differentiation during development (Laurent, 1998).…”

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confidence: 99%

“…HA is known to be involved in wound healing, promoting cell motility and differentiation during development (Laurent, 1998). A number of strategies for the chemical modification of HA for improving its physicochemical properties through carboxyl and hydroxyl groups have been developed (Balazs and Leshchiner, 1987;Kuo et al, 1991;Illum et al, 1994;Luo et al, 2000;Hahn et al, 2004;Ohri et al, 2004).…”

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Hyaluronic Acid in Drug Delivery Systems

Jin¹,

Termsarasab²,

Kim³

2010

Journal of Pharmaceutical Investigation

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− Hyaluronic acid (HA) is a biodegradable, biocompatible, non-toxic, non-immunogenic and non-inflammatory linear polysaccharide, which has been used for various medical applications including arthritis treatment, wound healing, ocular surgery, and tissue augmentation. Because of its mucoadhesive property and safety, HA has received much attention as a tool for drug delivery system development. It has been used as a drug delivery carrier in both nonparenteral and parenteral routes. The nonparenteral application includes the ocular and nasal delivery systems. On the other hand, its use in parenteral systems has been considered important as in the case of sustained release formulation of protein drugs through subcutaneous injection. Particles and hydrogels by various methods using HA and HA derivatives as well as by conjugation with other polymer have been the focus of many studies. Furthermore, the affinity of HA to the CD44 receptor which is overexpressed in various tumor cells makes HA an important means of cancer targeted drug delivery. Current trends and development of HA as a tool for drug delivery will be outlined in this review.

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“…The mechanism of drug release operates independently of the device geometry and another possibility of drug release by physically incorporating the drug in the HYAFF ® membrane. The use of HYAFF ® 11 microspheres loaded with insulin produced large and significant increases in the nasal membrane absorption of peptides [21]. The absorption-enhancing properties of HYAFF ® are related to bioadhesiveness, the appropriate size range of the microspheres, and the release of the drug from biomaterials, but did not induce mucosal damage applied in the local lesions [6-8, 14, 15, 23, 24, 34, 38, 39].…”

Section: Hyaluronan Esters In Drug Delivery Devices and Mesenchymamentioning

confidence: 99%