Evaluation of burst release and sustained release of pioglitazone-loaded fibrous mats on diabetic wound healing: an in vitro and in vivo comparison study

Abstract

In order to provide more effective treatment strategies for the rapid healing of diabetic wounds, novel therapeutic approaches need to be developed. The therapeutic potential of peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist pioglitazone hydrochloride (PHR) in two different release kinetic scenarios, burst release and sustained release, was investigated and compared with in vitro and in vivo tests as potential wound healing dressings. PHR-loaded fibrous mats were successfully fabricated using polyvinyl-pyrrolidone and polycaprolactone by scalable pressurized gyration. The results indicated that PHR-loaded fibrous mats expedited diabetic wound healing in type-1 diabetic rats and did not show any cytotoxic effect on NIH/3T3 (mouse embryo fibroblast) cells, albeit with different release kinetics and efficacies. The wound healing effects of fibrous mats are presented with histological and biochemical evaluations. PHR-loaded fibrous mats improved neutrophil infiltration, oedema, and inflammation and increased epidermal regeneration and fibroblast proliferation, but the formation of hair follicles and completely improved oedema were observed only in the sustained release form. Thus, topical administration of PPAR-γ agonist in sustained release form has high potential for the treatment of diabetic wounds in inflammatory and proliferative phases of healing with high bioavailability and fewer systemic side effects.

Engineered Microneedle Patches for Controlled Release of Active Compounds: Recent Advances in Release Profile Tuning

“…Another advantage of controlled drug release is improved patient compliance due to less frequent drug administration. [ 41–43 ] Microneedles may be classified into three categories based on their release profiles: burst release, prolonged release, and on‐demand release. Rapid drug release from polymeric systems is coined “burst or instant release.” [ 44 ] This kind of release is necessary for applications such as analgesic delivery, when rapid release of a therapeutic agent is essential.…”

“…For therapeutic agents such as those utilized at the beginning of wound healing, an initial burst release offers almost instantaneous relief, which is followed by sustained release to accelerate healing. [ 41 ]…”

“…For therapeutic agents such as those utilized at the beginning of wound healing, an initial burst release offers almost instantaneous relief, which is followed by sustained release to accelerate healing. [41] Microneedles with burst release profiles involve the use of highly dissolvable and water-soluble polymeric matrices. These polymeric matrices undergo fast dissolution (i.e., within several Figure 2.…”

Innate Immunity in Diabetic Wound Healing: Focus on the Mastermind Hidden in Chronic Inflammatory

“…Besides, PPARγ agonists can also down-regulate the expression of TLR4 (Ji et al, 2009). Using Pioglitazone-loaded fibrous mats which are prepared from pioglitazone hydrochloride (PHR) on the wound of DM rats, it is found that both burst-release and sustained-release kinetics can down-regulate the expression of TNF-α and promote DW healing, but the sustained-release form is more effective in reducing PMNs infiltration and inflammation, promoting epidermal regeneration and fibroblast proliferation (Cam et al, 2020), Similarly, topically using GQ-11 (a partial/dual PPAR α/γ agonist) and Pioglitazone on the wound of DM mice can also downregulate IL-1β and TNF-α, promote DW healing (Silva et al, 2019). An in-depth understanding of the relationship between TLR signaling pathways and drug regulation targets, as well as the impact of different types of drugs on drug delivery and efficacy, can provide a feasible direction for the treatment of DW.…”

The comparision of glybenclamide and metformin-loaded bacterial cellulose/gelatin nanofibres produced by a portable electrohydrodynamic gun for diabetic wound healing

“…hyperglycemia, promotes a proinflammatory phenotype of macrophages. These macrophages, purposed with killing pathogens and removing damaged tissue, release pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) at a sustained level, preventing the progression of the healing process and the consequent release of antiinflammatory cytokines and growth factors [4][5][6]. There has also been research investigating the persistent presence of cytokine precursors; such as Nod-like receptor protein (NLRP3) and caspase-1, in diabetic wounds disrupting the healing process [7].…”