Long-Term Toxicity Study of Topical Administration of a Highly-Stable rh-aFGF Carbomer 940 Hydrogel in a Rabbit Skin Wound Model

Abstract

We developed a highly stable recombinant human acidic fibroblast growth factor (rh-aFGF) carbomer 940 hydrogel for wound healing. This study aimed to reveal toxicity target organs and the toxicity dose-response in the long-term administration of rh-aFGF carbomer 940 hydrogel in a rabbit skin wound model. New Zealand rabbits were topically administrated rh-aFGF carbomer 940 hydrogel at a daily dose of 900 IU/cm 2 , 1,800 IU/cm 2 , and 3,600 IU/cm 2 for 28 days. Lyophilized rh-aFGF agent was used as the positive control group. General behavior, serum chemistry, skin irritation, immunogenicity, immunotoxicity, and histopathology were analyzed at designated time points. Results revealed that food intake, body weight, body temperature, heart rate, and eye examinations were all normal, suggesting no obvious toxicity induced by the rh-aFGF hydrogel. Medium and high dose rh-aFGF hydrogel groups and the positive control group displayed increased cell numbers in the local lymph nodes near the site of administration, likely caused mesenteric lymph node follicular hyperplasia, and this observation was alleviated after 14 days of recovery. Immunogenicity studies demonstrated that the serum antibody titer against rh-aFGF increased with the duration and number of drug applications but were not neutralization antibodies. After administration stopped, antibody titer decreased and disappeared in some mice. In summary, the safe dose for long-term administration of rh-aFGF carbomer 940 hydrogel for persistently damaged skin was 900 IU/cm 2 , which is 10 times that of the proposed clinical dosing.

Log P Determines Licorice Flavonoids Release Behaviors and Classification from CARBOMER Cross-Linked Hydrogel

“…As one of the successfully controlled release vehicles, Carbomer 940 (CP) hydrogel is still known as a thickener in topical preparations due to its moderate rheological properties and high storage stability [ 15 , 16 ]. Drug release from hydrogels involves the hybridization of hydrogel relaxation (or hydrogel degradation) and drug diffusion; usually, more than one mechanism controls drug release in a release system.…”

Topical recombinant human acidic fibroblast growth factor: An effective therapeutic agent for facemask wearing‐induced pressure sores

“…However, there was a research demonstrated that the high-dose, repeated rh-aFGF application did not cause excessive repair of the tissue or scarring. 8 Moreover, the research also demonstrated that no obvious toxicity to the target organs and tissues was observed during the repeated treatment of rh-aFGF. 8 These results were consistent with our survey feedback that no health care workers have claimed any discomfort or scarring happened during the use of rh-aFGF.…”

“…Considering that rh‐aFGF can increase the expression of collagen and muscle fibers, resulting in enhanced tissue remodeling, 6 a worry that whether excessive tissue repair after long‐term repeated rh‐aFGF application would result in scar formation was raised. However, there was a research demonstrated that the high‐dose, repeated rh‐aFGF application did not cause excessive repair of the tissue or scarring 8 . Moreover, the research also demonstrated that no obvious toxicity to the target organs and tissues was observed during the repeated treatment of rh‐aFGF 8 .…”

Lidocaine-loaded reduced graphene oxide hydrogel for prolongation of effects of local anesthesia: In vitro and in vivo analyses

“…The rationale of performing the rabbit skin irritation study was to assess the possible local side effects, including discomfort, erythema, and edema associated with the developed lidocaine-loaded Pluronic® F68-rGO hydrogel. 51,52 The animals were grouped into hydrogel and placebo gel groups (n = 3), and a dorsal skin area of 2.5 × 2.5 cm 2 was cleaned with a razor and alcohol. After 6 h, the selected lidocaine-loaded Pluronic® F68-rGO hydrogel (Ld-rGO-100) or placebo hydrogel (Ld-Gel) was applied to the right dorsal area of the rabbits; the left dorsal area was considered as the control (without any gel).…”