Accelerating Payload Release from Complex Coacervates through Mechanical Stimulation

Abstract

Complex coacervates formed through the association of charged polymers with oppositely charged species are often investigated for controlled release applications and can provide highly sustained (multi-day, -week or -month) release of both small-molecule and macromolecular actives. This release, however, can sometimes be too slow to deliver the active molecules in the doses needed to achieve the desired effect. Here, we explore how the slow release of small molecules from coacervate matrices can be accelerated through mechanical stimulation. Using coacervates formed through the association of poly(allylamine hydrochloride) (PAH) with pentavalent tripolyphosphate (TPP) ions and Rhodamine B dye as the model coacervate and payload, we demonstrate that slow payload release from complex coacervates can be accelerated severalfold through mechanical stimulation (akin to flavor release from a chewed piece of gum). The stimulation leading to this effect can be readily achieved through either perforation (with needles) or compression of the coacervates and, besides accelerating the release, can result in a deswelling of the coacervate phases. The mechanical activation effect evidently reflects the rupture and collapse of solvent-filled pores, which form due to osmotic swelling of the solute-charged coacervate pellets and is most pronounced in release media that favor swelling. This stimulation effect is therefore strong in deionized water (where the swelling is substantial) and only subtle and shorter-lived in phosphate buffered saline (where the PAH/TPP coacervate swelling is inhibited). Taken together, these findings suggest that mechanical activation could be useful in extending the complex coacervate matrix efficacy in highly sustained release applications where the slowly releasing coacervate-based sustained release vehicles undergo significant osmotic swelling.

Keywords: complex coacervate; controlled release; polyamine; polyelectrolyte; stimulus-responsive materials.

Figure 1

Mechanical stimulation schemes showing the approximate locations of the (a) perforations by the 5 needle jabs and (b) compressive spatula insertions. The perforated samples were jabbed multiple times during each treatment, while those subjected to compression were compressed once per treatment, either on the front, back, left, or right side of the sample.

Figure 2

RhB release from coacervates into deionized water achieved with (■) periodic perforation by five needle jabs, (●) periodic compression, and (♦) without mechanical stimulation and shown in terms of both (a) the total RhB mass released and (b) the release rate (mean ± SD). The inset provides a closeup of the slower release rates near the end of the experiment. The coacervates in this experiment were stimulated every 3 d using either five needle jabs or a spatula. The solid lines are guides to the eye, while the dashed vertical lines mark the mechanical stimulation times.

Figure 3

Coacervate swelling during the RhB release into deionized water achieved with (■) periodic perforation, (●) periodic compression, and (♦) without mechanical stimulation and characterized by (a) gravimetric analysis of the evolutions in normalized weights (mean ± SD) and (b) digital photography (i) without mechanical stimulation, (ii) with periodic perforation, and (iii) periodic compressions. Also shown are (c) a top view of a coacervate sample after a perforation treatment and (d) schemes of the solvent-filled pores collapsing after each mechanical treatment. The coacervates in this experiment were stimulated every 3 d using either five needle jabs or a spatula. All coacervate weights are normalized to their initial values at the start of the release experiment. The solid lines are guides to the eye, while the dashed vertical lines mark the mechanical stimulation times.

Figure 4

RhB release from coacervates into deionized water achieved with (■) daily perforation with two needle jabs, (●) daily compression, and (♦) without mechanical stimulation and shown in terms of both (a) the total RhB mass released and (b) the release rate (mean ± SD). The inset provides a closeup of the slower release rates near the end of the experiment, while the lines are guides to the eye.

Figure 5

Swelling of coacervates during RhB release into deionized water achieved with (■) daily perforation by two needle jabs, (●) daily compression, and (♦) without mechanical stimulation and characterized by (a) gravimetric analysis of the evolutions in normalized weights (mean ± SD) and (b) digital photography (i) without mechanical stimulation, (ii) with periodic perforation, and (iii) periodic compression. All coacervate weights are normalized to their initial values at the start of the release experiment. The lines are guides to the eye.

Figure 6

Coacervate swelling in 1 × PBS with (■) daily perforation with five needle jabs, (●) daily compression, and (♦) without mechanical stimulation and characterized by (a) gravimetric analysis of the evolutions in normalized weights (mean ± SD) and (b) digital photography (i) without mechanical stimulation, (ii) with periodic perforation, and (iii) with periodic compression. All coacervate weights are normalized to their initial values at the start of the release experiment. The lines are guides to the eye.

Figure 7

RhB release from coacervates into 1 × PBS achieved with (■) daily perforation with five needle jabs, (●) daily compression, and (♦) without mechanical stimulation and shown in terms of both (a) the total RhB mass released and (b) the release rate (mean ± SD). The inset provides a closeup of the slower release rates near the end of the experiment, while the lines are guides to the eye.