Abstract
Aim: The aim of the present investigation entails the development and evaluation of a topical nanoemulgel formulation of tazarotene for the effective treatment of excision wounds.
Background: Tazarotene (TZR) is a retinoid derivative marketed for the treatment of acne and psoriasis and recent investigations indicate its excellent wound healing potential. Despite having magnificent wound healing potential, it suffers from pharmacokinetic limitations of low aqueous solubility and local bioavailability. Conventional marketed formulations of TZR have been reported to cause significant skin irritation and redness after its topical application. Keeping this in view, the present investigation was designed to develop nanoemulsion based gel with the intention to resolve the above mentioned pharmacokinetic and pharmacodynamic issues.
Objective: The goal of the study was to develop a stable and effective tazarotene-loaded nanoemulgel for treating excision wounds, which can also overcome the issues associated with the native drug.
Methods: Various oils, surfactants and co-surfactants were selected on the basis of their solubilisation potential for tazarotene. Pseudoternary phase plots were constructed to obtain a stable nanoemulsion region for various proportions of oil, surfactant: co-surfactant (Smix) and water and to determine optimized concentration ranges for the robust formulation of tazarotene. Various characterization parameters were studied to investigate the optimized formulation having desired attributes of nanoemulsion. Reducing power assay and phamacodymanic studies were conducted to determine the wound healing potential of developed nanoemulgel.
Results: TZR loaded nanoemulsion was successfully developed with nano-sized globules using tea tree oil with Tween 20 as surfactant and PEG 400 as co-surfactant. Prepared nanoemulsions were thermodynamically stable and were further gellified using Carbopol 940 as a biodegradable gelling polymer. Prepared gels showed good spreadability, drug permeation and stability. In vivo investigations demonstrated that optimized formulation successfully masked the irritant nature of tazarotene. Moreover, the pharmacodynamic evaluation of the developed nanoemulsion gel revealed its significant analgesic, anti-inflammatory properties in addition to its markable wound contraction as compared to control.
Conclusion: The results demonstrated the potential of developed nanoemulgel over marketed formulation to overcome the drawbacks like redness and erythema. It also showed significant healing efficacy over other tested formulations owing to the synergistic activity of tazarotene and tea tree oil encapsulated in the nanoemulsion system.
Keywords: Tazarotene, Wounds, Anti-inflammatory, Nanoemulsion, Nanoemulgel, Antioxidant
Graphical Abstract
[http://dx.doi.org/10.1089/wound.2019.0946] [PMID: 30809421]
[http://dx.doi.org/10.1016/j.jep.2006.05.011] [PMID: 16806763]
[http://dx.doi.org/10.1016/j.ejpb.2012.11.022] [PMID: 23207329]
[http://dx.doi.org/10.1016/B978-0-12-813667-6.00014-0]
[http://dx.doi.org/10.1038/mt.2016.153] [PMID: 27480772]
[http://dx.doi.org/10.1016/j.adengl.2012.09.014] [PMID: 22818395]
[http://dx.doi.org/10.1016/S0190-9622(98)70310-X]
[http://dx.doi.org/10.2174/1876402907666151103210822]
[http://dx.doi.org/10.1097/BCR.0000000000000217] [PMID: 26182074]
[http://dx.doi.org/10.1023/A:1015854728278] [PMID: 1475228]
[http://dx.doi.org/10.2217/nnm.10.126] [PMID: 21143036]
[http://dx.doi.org/10.1016/S0168-3659(00)00309-6] [PMID: 11018558]
[http://dx.doi.org/10.1517/17425247.2016.1162154] [PMID: 26984045]
[http://dx.doi.org/10.1016/j.ijfoodmicro.2004.03.022] [PMID: 15246235]
[http://dx.doi.org/10.1021/jf035377d] [PMID: 15137824]
[http://dx.doi.org/10.1111/j.1365-4632.2012.05654.x] [PMID: 22998411]
[http://dx.doi.org/10.1128/AAC.46.6.1914-1920.2002] [PMID: 12019108]
[http://dx.doi.org/10.1155/2016/9702129] [PMID: 27689094]
[http://dx.doi.org/10.1016/0378-5173(94)00222-Q]
[http://dx.doi.org/10.1016/j.wndm.2018.01.003]
[http://dx.doi.org/10.4103/1687-4315.197586]
[http://dx.doi.org/10.3109/10611860903548362] [PMID: 20067438]
[http://dx.doi.org/10.1016/j.ijbiomac.2017.03.066] [PMID: 28322948]
[http://dx.doi.org/10.1016/j.fjps.2017.07.003]
[http://dx.doi.org/10.1016/j.fbio.2019.01.018]
[http://dx.doi.org/10.1021/jf0103572] [PMID: 11513714]
[http://dx.doi.org/10.1007/s13197-012-0804-y] [PMID: 26396344]
[http://dx.doi.org/10.15171/apb.2015.043] [PMID: 26504751]
[http://dx.doi.org/10.3109/10717544.2014.893382] [PMID: 24625264]
[http://dx.doi.org/10.22159/ajpcr.2017.v10i8.19510]
[http://dx.doi.org/10.3109/08982104.2014.995670] [PMID: 25547800]
[http://dx.doi.org/10.1016/j.ijvsm.2017.10.002] [PMID: 30255061]
[http://dx.doi.org/10.1016/S0378-5173(00)00614-1] [PMID: 11165081]
[http://dx.doi.org/10.1016/j.jconrel.2017.03.008] [PMID: 28279798]
[http://dx.doi.org/10.3390/molecules26133863] [PMID: 34202733]
[http://dx.doi.org/10.1016/j.biopha.2019.108622] [PMID: 30797146]
[http://dx.doi.org/10.1016/j.xphs.2018.07.015] [PMID: 30055224]
[http://dx.doi.org/10.1007/s12010-016-2099-3] [PMID: 27179517]
[http://dx.doi.org/10.3390/pharmaceutics14061133] [PMID: 35745706]
[http://dx.doi.org/10.1046/j.1523-1747.2003.12359.x] [PMID: 12880413]
[http://dx.doi.org/10.1080/10837450.2020.1765180] [PMID: 32364036]
[http://dx.doi.org/10.1097/DSS.0000000000000819] [PMID: 27347634]
[http://dx.doi.org/10.2119/molmed.2009.00153] [PMID: 20927486]