Publications by authors named "Joao Pedro Garcia"

Intradiscal drug delivery is a promising strategy for treating intervertebral disk degeneration (IVDD). Local degenerative processes and intrinsically low fluid exchange are likely to influence drug retention. Understanding their connection will enable the optimization of IVDD therapeutics.

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Chronic lower back pain caused by intervertebral disc degeneration and osteoarthritis (OA) are highly prevalent chronic diseases. Although pain management and surgery can alleviate symptoms, no disease-modifying treatments are available. mRNA delivery could halt inflammation and degeneration and induce regeneration by overexpressing anti-inflammatory cytokines or growth factors involved in cartilage regeneration.

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Article Synopsis
  • This study focuses on developing poly(lactide-co-glycolide) (PLGA) nanoparticles decorated with hyaluronic acid (HA) to improve targeted drug delivery for osteoarthritis treatment.
  • HA is significant for its ability to bind to CD44 receptors found in cartilage cells, ensuring the nanoparticles reach the osteoarthritic knee joint effectively.
  • The results indicated that PLGA-HA nanoparticles had greater affinity for cartilage cells, suggesting a safer and more effective drug delivery system compared to traditional methods.
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Osteoarthritis (OA) is a highly prevalent disease and a major health burden. Its development and progression are influenced by factors such as age, obesity or joint overuse. As a whole organ disease OA affects not only cartilage, bone and synovium but also ligaments, fatty or nervous tissue surrounding the joint.

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Pro-inflammatory cytokines are considered to play a major role in osteoarthritis (OA), yet so far, the specific cytokines involved in the pathology of OA have not been identified. Oncostatin M (OSM) is a cytokine from the interleukin 6 (IL-6) family that has been shown to be elevated in synovial fluid of most rheumatoid arthritis (RA) patients, but only in a limited subset of OA patients. Little is known about OSM in the different joint tissues during OA and how its expression correlates with hallmarks of disease.

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Osteoarthritis (OA) and intervertebral disc degeneration (IVDD) as major cause of chronic low back pain represent the most common degenerative joint pathologies and are leading causes of pain and disability in adults. Articular cartilage (AC) and intervertebral discs are cartilaginous tissues with a similar biochemical composition and pathophysiological aspects of degeneration. Although treatments directed at reversing these conditions are yet to be developed, many promising disease-modifying drug candidates are currently under investigation.

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To date no disease-modifying drugs for osteoarthritis (OA) are available, with treatment limited to the use of pain killers and prosthetic replacement. The ADAMTS (A Disintegrin and Metallo Proteinase with Thrombospondin Motifs) enzyme family is thought to be instrumental in the loss of proteoglycans during cartilage degeneration in OA, and their inhibition was shown to reverse osteoarthritic cartilage degeneration. Locked Nucleic Acid (LNA)-modified antisense oligonucleotides (gapmers) released from biomaterial scaffolds for specific and prolonged ADAMTS inhibition in co-delivered and resident chondrocytes, is an attractive therapeutic strategy.

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One important drawback of most of the currently used dendrimers for biomedical applications is their high stability under physiological conditions that can result in cytotoxicity or complications induced by the accumulation of non-degradable synthetic materials in the organism. Particularly in the gene therapy field, vector stability can further hinder the intracellular release of the nucleic acid from the dendriplex, consequently leading to low transfection efficiencies. Therefore, biodegradable cationic dendritic structures have been eagerly awaited.

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Interest in dendrimer-based nanomedicines has been growing recently, as it is possible to precisely manipulate the molecular weight, chemical composition, and surface functionality of dendrimers, tuning their properties according to the desired biomedical application. However, one important concern about dendrimer-based therapeutics remains-the nondegradability under physiological conditions of the most commonly used dendrimers. Therefore, biodegradable dendrimers represent an attractive class of nanomaterials, since they present advantages over conventional nondegradable dendrimers regarding the release of the loaded molecules and the prevention of bioaccumulation of synthetic materials and subsequent cytotoxicity.

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