Green preparation, charetrization, in vitro/in vivo safety assessment and in vivo pain management of nortriptyline HCl loaded in niosome (norosome) manufactured by ecofriendly green method

Pain is an unfavorable feeling that is generally triggered by endogenous or exogenous harmful stimulation and has a strong emotional impact. The objective of this experimentation was to increase the cutaneous absorption of nortriptyline HCl (NOR) encapsulated in a niosome (norosomes) produced by an ultrasonic approach for the management of antinociceptive and anti-inflammatory disorders. Exploring the implications of the cholesterol:surfactant ratio on norosome compositions, the study revealed that increasing cholesterol significantly enlarged the norosome diameter from 66.84 +/- 5.70 to 293.06 +/- 36.54 nm (p < 0.05). More research revealed that changes in the cholesterol:surfactant ratio could influence the surface charge (19.27 +/- 0.89 to 16.30 +/- 0.78 mV) and entrapment efficiency (EE%) (7.90 +/- 1.59 to 87.44 +/- 2.11%) (p < 0.05). The amorphous nature of NOR in the niosome was shown by solid-state research. The dermal absorption study revealed that NOR was present at larger levels in dermal layers (41.79 +/- 2.38%) and the receiver area (28.67 +/- 1.33%) for norosome gel than for NOR-Carbopol gel. The norosomal's cell safety was 84%, and the MTT study indicated a reduction in norosome cytotoxicity. The skin irritation analysis conducted on Wistar rats showed that the niosome component used did not cause irritation to the skin. Eventually, in comparison to the control group, norosome formulation demonstrated significant antinociceptive and anti-inflammatory (246.16 +/- 53.60 s) actions in the late stage formalin test, tail-flick latency (5.18 +/- 0.18 s), and hot plate latency (12.57 +/- 1.78 s) (p < 0.05). These findings suggest that niosomes have the potential to enhance the effectiveness of NOR as an antinociceptive and anti-inflammatory agent by improving drug delivery to the targeted site.