Investigating the Relationship Between the Emulsification Parameters and Physical-Chemical Properties of Poly(D,L-lactic acid) Particles for Dermal Fillers

Abstract

Poly(L-lactic acid) (PLLA) and poly(D,L-lactic acid) (PDLLA) particles have been applied as dermal fillers for soft-tissue augmentation because they can induce foreign-body reactions, resulting in fibroblast proliferation and collagen formation. Although PLLA and PDLLA fillers are safe and biocompatible, clinical complications such as nodules and granulomas have been reported, possibly due to incomplete reconstitution. PDLLA particles were prepared via emulsification in this study, and three stirring speeds were investigated when adding PDLLA into carboxymethyl cellulose solution. The particle size, molecular weight of PDLLA, optical rotation, pH value, osmotic pressure, and reconstitution time were analyzed. A rabbit dorsal ear model was established to evaluate the soft-tissue augmentation of a commercial PDLLA filler. The results demonstrated that the stirring speed affected the particle size, but not other physical-chemical properties of the PDLLA particles. All the PDLLA particles were reconstituted in less than 7 min, which is faster than the process for the other commercial PDLLA dermal filler products. In addition, the PDLLA particles could induce inflammation and fibroblast proliferation. Although the PDLLA particles generated in this study have not yet been investigated in vivo, the results demonstrated here suggest their potential for application as dermal fillers.

Keywords: carboxymethyl cellulose; dermal filler; emulsification; poly(D,L-lactic acid) acid particle; reconstitution; soft-tissue augmentation.

Figure 1

A picture of reconstitution testing (a) when distilled water was added to a vial of PDLLA particles immediately or (b) after all the particles had dissolved and dispersed.

Figure 2

Scanning electronic microscope images of PDLLA particles that were generated at stirring speeds of 100 rpm (a), 200 rpm (b), or 400 rpm (c), as well as a commercial NeoFilera PDLLA product (d). Scale bar shows 50 μm with 100× magnification and 10 μm with 500× magnification.

Figure 3

Characteristics of functional groups in various PDLLA particles (100, 200, or 400 rpm) and commercial NeoFilera PDLLA particles.

Figure 4

Inflammation scores of injected sites in normal saline or NeoFilera PDLLA particle groups at 12 weeks (white bars) or 26 weeks (black bars) post-injection. * p < 0.05 when comparing inflammation scores in normal saline at 12 weeks vs. 26 weeks post-injection. # p < 0.05 when comparing inflammation scores in normal saline vs. NeoFilera PDLLA particle groups at same time point.

Figure 5

Histological analysis of hematoxylin and eosin (H&E) or Masson’s trichrome (MT) staining after injecting normal saline (a,c) or NeoFilera PDLLA particles (b,d) for 12 or 26 weeks.