TY - JOUR
T1 - Quality-by-Design Approach for the Development of Nano-Sized Tea Tree Oil Formulation-Impregnated Biocompatible Gel with Antimicrobial Properties
AU - Muta, Thabata
AU - Parikh, Ankit
AU - Kathawala, Krishna
AU - Haidari, Hanif
AU - Song, Yunmei
AU - Thomas, Jackson
AU - Garg, Sanjay
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/11/13
Y1 - 2020/11/13
N2 - Despite the promising properties of tea tree oil (TTO) as potential therapeutics for several superficial skin conditions, certain limitations such as physical instability and skin irritation have restricted its widespread use. This study focuses on developing a rationally designed lipid-based nanoformulation (TTO-LNF) in accordance with the US Food and Drug Administration standard using a well-recognized quality-by-design (QbD) approach. Using a mixture experimental design, TTO-LNF has been optimized with 5% TTO, 10% surfactant, 5% co-surfactant, and 80% water, which showed a 14.4 ± 4.4 nm droplet size and 0.03 ± 0.01 polydispersity index (PDI). To ease the topical administration, the TTO-LNF gel formulation was further developed using xanthan gum to achieve the desired viscosity and form a gel. The in vitro antibacterial tests of TTO-LNF showed promising inhibitory effects toward both Gram-negative and Gram-positive bacteria. In fact, a complete growth inhibition of S. epidermidis was observed when exposed to TTO-LNF and TTO-LNF gel for 24 h, showing better activity than antibiotic kanamycin (25 µg/mL). Additionally, the in vitro release study showed a sustained release profile with a 50% release in 24 h, which could be beneficial to reduce the toxicity and thereby improve the therapeutic efficacy for long-acting applications. Furthermore, the formulations were remarkably stable at 40 °C/75% Relative humidity (RH) for at least 4 weeks. Therefore, this study presents a promising strategy to develop a biocompatible and stable formulation that can be used for the topical treatment of skin infections.
AB - Despite the promising properties of tea tree oil (TTO) as potential therapeutics for several superficial skin conditions, certain limitations such as physical instability and skin irritation have restricted its widespread use. This study focuses on developing a rationally designed lipid-based nanoformulation (TTO-LNF) in accordance with the US Food and Drug Administration standard using a well-recognized quality-by-design (QbD) approach. Using a mixture experimental design, TTO-LNF has been optimized with 5% TTO, 10% surfactant, 5% co-surfactant, and 80% water, which showed a 14.4 ± 4.4 nm droplet size and 0.03 ± 0.01 polydispersity index (PDI). To ease the topical administration, the TTO-LNF gel formulation was further developed using xanthan gum to achieve the desired viscosity and form a gel. The in vitro antibacterial tests of TTO-LNF showed promising inhibitory effects toward both Gram-negative and Gram-positive bacteria. In fact, a complete growth inhibition of S. epidermidis was observed when exposed to TTO-LNF and TTO-LNF gel for 24 h, showing better activity than antibiotic kanamycin (25 µg/mL). Additionally, the in vitro release study showed a sustained release profile with a 50% release in 24 h, which could be beneficial to reduce the toxicity and thereby improve the therapeutic efficacy for long-acting applications. Furthermore, the formulations were remarkably stable at 40 °C/75% Relative humidity (RH) for at least 4 weeks. Therefore, this study presents a promising strategy to develop a biocompatible and stable formulation that can be used for the topical treatment of skin infections.
KW - Accelerated stability assessment
KW - Anti-microbial activity
KW - Controlled release
KW - Lipid-based nanotechnology
KW - Mixture experimental design
KW - Pseudomonas aeruginosa
KW - Quality by design
KW - Staphylococcus epidermidis
KW - Tea tree oil
KW - Topical drug delivery
UR - http://www.scopus.com/inward/record.url?scp=85096064259&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics12111091
DO - 10.3390/pharmaceutics12111091
M3 - Article
C2 - 33202841
SN - 1999-4923
VL - 12
SP - 1
EP - 16
JO - Pharmaceutics
JF - Pharmaceutics
IS - 11
M1 - 1091
ER -