Osteoarthritisis the most prevalent rheumatic disorder affecting the musculoskeletal system;
osteoarthritis is a degenerative form of arthritis that results in gradually
breakdown of joint cartilage; osteoarthritis can be also viewed as an
inflammatory disease. Currently applied therapies consist of physical therapy,
oral medication, intra-articular injections and surgical interventions, their
main goal being to reduce pain and improve function and quality of life.
Intra-articular administration of drugs has potential benefits in
osteoarthritis treatment because it minimizes systemic bioavailability and side
effects associated with oral administration of drugs and enhances their
therapeutic effect in the joint. However, the residence time of the drug is short
and several drug delivery systems were explored to obtain a sustained release.
This review is focused on the use of chondroitin sulfate as bioactive molecule
in the treatment of osteoarthritis and the liposome ability as suitable drug
delivery system for chondroitin sulfate.
Osteoarthritis (OA) is a degenerative disease, but not a
systemic one, characterized by progressive loss of articular cartilage,
subchondral bone sclerosis and osteophyte formation, changes in the synovial
membrane and increased volume of synovial fluid with altered coefficient of
friction. In some aspects, it can be also viewed as an inflammatory
disease, leading to chronic pain and decrease of life quality. Presently,
there is no prevention or efficient treatment that can stop the pathological processes
involved in OA progression, since available treatments are directed to
symptoms, pain relieve and function regain. The administration of
nonsteroidal Anti-Inflammatory Drugs (NSAIDs), analgesics compounds and
corticosteroids is achieved through oral, parenteral or intra-articular
(i.a.) route, targeting to reduce or revise joint damage and inflammation.
The oral drug administration has major disadvantages, such as
limited bioavailability and risk of side effects. As OA has a localized nature,
i.a. administration of drugs provides the opportunity to improve the treatment
by local depot formation and prolonged drug action. To treat local
diseases, like joint disorders, i.a. route is very useful. However, the
efficacy of i.a. administration of different anti-inflammatory bioactive
molecules (e.g., glycoproteins, proteoglycans) is limited due to their poor
stability and delivery in the harmful biological milieu. Several
delivery systems, including liposomes, microparticles, nanoparticles and
hydrogels have been investigated for the sustained drug delivery and for
prolonged drug release in the joints. In vitro studies have demonstrated
that the phospholipidic layer acting as a boundary lubricant was missing from
the articular surface of osteoarthritic degenerated cartilage and changes in
the structure of Chondroitin Sulfate (CS) occurred in case of OA
This
review highlighted the advantages offered by liposomes as i.a. delivery system
in treatment of OA. Data regarding the physico-chemical properties,
biocompatibility, anti-inflammatory and regenerative potential of the liposomal
formulations of CS are summarized. It is also discussed the trend in i.a.
therapy of arthritis using this promising technology.
Intra-articular
(i.a.) therapy improves drug delivery to joint cartilage and thus, it can
increase the therapeutic efficacy in OA treatment by minimizing systemic
bioavailability and side effects associated with oral administration. A very
well structured review of Evans et al. presented the progress, clinical
performances and advantages of i.a. therapy of arthropaties. Being
discrete cavities, most diarthrodial joints are well suited for the local drug
delivery via i.a. injection. The advantages offered by i.a. delivery of
therapeutics in diarthrodial joints are also presented by Chen & Yang. They
have noticed the importance of delivering drugs not just on the surface of the
articular cartilage, but also into its matrix, in order to obtain a deeper zone
treatment. Moreover, it should be fully considered that the drug
biodistribution following delivery is quite different in i.a. administration
from systemic administration or local injection into other tissues or organs.
Many corticosteroid formulations are available for i.a. injection in OA and
several studies have compared their effectiveness in OA. The conclusion was
that they offer a shortterm solution for a chronic problem, reducing pain in
the knee for at least 1 week. An alternative treatment for joints affected
by OA that have not responded to NSAIDs or analgesics is the i.a.
administration of natural bioactive substances that can influence the
pathophysiology of OA joints, such as lubricin, also known as proteoglycan and hyaluronate, a component of the cartilage extracellular matrix
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