Composing On-Program Triggers and On-Demand Stimuli into Biosensor Drug Carriers in Drug Delivery Systems for Programmable Arthritis Therapy

Abstract

Medication in arthritis therapies is complex because the inflammatory progression of rheumatoid arthritis (RA) and osteoarthritis (OA) is intertwined and influenced by one another. To address this problem, drug delivery systems (DDS) are composed of four independent exogenous triggers and four dependent endogenous stimuli that are controlled on program and induced on demand, respectively. However, the relationships between the mechanisms of endogenous stimuli and exogenous triggers with pathological alterations remain unclear, which results in a major obstacle in terms of clinical translation. Thus, the rationale for designing a guidance system for these mechanisms via their key irritant biosensors is in high demand. Many approaches have been applied, although successful clinical translations are still rare. Through this review, the status quo in historical development is highlighted in order to discuss the unsolved clinical difficulties such as infiltration, efficacy, drug clearance, and target localisation. Herein, we summarise and discuss the rational compositions of exogenous triggers and endogenous stimuli for programmable therapy. This advanced active pharmaceutical ingredient (API) implanted dose allows for several releases by remote controls for endogenous stimuli during lesion infections. This solves the multiple implantation and local toxic accumulation problems by using these flexible desired releases at the specified sites for arthritis therapies.

Keywords: biosensors; drug carriers; drug delivery systems; endogenous stimuli; exogenous triggers; pathological alterations.

Figure 1

Timeline of significant discoveries and advancements in drug delivery systems with drug carriers, on-demand stimuli, and on-program triggers.

Figure 2

The mechanisms of multiple on-program triggers are enhanced with multiple on-demand stimuli to release API for arthritis diseases.

Figure 3

The photothermal triggers with magnetic targetors add redox and pH biosensors in drug carriers to release API. The first and second flows from drug carriers to API are shown in dark blue and light blue, respectively.

Figure 4

The magnetothermal triggers added with either redox, pH, or both stimuli into biosensors in drug carriers to release API.

Figure 5

The sonodynamical trigger with either redox or electro-ion stimuli added into their biosensors in drug carriers to release API. The flows from drug carriers to API are represented by the first and third cells, and second cells, as shown in dark blue and light blue, respectively.

Figure 6

The electrical biosensors are triggered to release API in drug carriers that are made of MOFs and conductive polymers.

Figure 7

The enzymatic stimulation mechanisms of biosensors in drug carrier use MMP-2 and MMP-9 [158,167] to cleave peptide sites for API release in arthritis treatment. Reprinted with permission.