The critical time window between the incidence of frostbite
injury
and the initiation of treatment in remote snowbound areas is a determining
factor for an effective therapeutic response. It is an emergency condition
and challenging to treat due to the poor vascularity of affected body
parts, and it requires immediate action. In addition to cold trauma-induced
tissue damage, the inflammatory mediators majorly contribute to pathologic
aggravations. We have designed and evaluated a topical “nano-spray
gel (NSG)” formulation, which is based on a combination of
liposomal heparin sodium (Hp) and ibuprofen (Ibu) for rapid relief
of frostbite injury in extremely low temperatures. The scientific
literature suggests that heparin is associated with rapid endothelial
cell repair, normalizing blood circulation in capillaries, and has
a potential role in wound healing. Hp-containing liposomes were prepared
by the extruder method, which suitably formulated an ibuprofen-containing
gel to obtain a nano-Spray formulation (HLp-Ibu-NSG) applicable for
topical delivery. A single spray puff of the formulation delivers
∼154 mg of the gel, which corresponds to ∼205 U of heparin.
In this study, heparin liposomes exhibited significant healing of
wound in vitro (scratch assay, fibroblast cells) and in vivo (wound
healing in Sprague Dawley rats) at a low dose. In the rat model of
frostbite injury, the HLp-Ibu-NSG formulation demonstrated significant
reduction in the wound area (up to ∼96%) and improvement of
histopathology in 14 days as compared to the control groups. No edema
and erythema were detected post-treatment of HLp-Ibu-NSG in the affected
area. The underlying mechanism was delineated as a modulation of the
inflammatory cytokine (IL-6, TNF-α, IL-10, IL-4) mediators at
the wound site and blood circulation to foster frostbite healing.
Future clinical studies on the nano-spray gel are required to evaluate
its efficacy for the treatment of frostbite symptoms. The instant
on-site application of this formulation might be helpful in saving
extremities of soldiers, mountaineers, and pilgrims having frostbite.
Host defense peptides (HDP) are small cationic molecules released by the immune systems
of the body, having multidimensional properties including anti-inflammatory, anticancer, antimicrobial
and immune-modulatory activity. These molecules gained importance due to their broad-spectrum
pharmacological activities, and hence being actively investigated. Presently, respiratory infections
represent a major global health problem, and HDP has an enormous potential to be used as an alternative
therapeutics against respiratory infections and related inflammatory ailments. Because of their
short half-life, protease sensitivity, poor pharmacokinetics, and first-pass metabolism, it is challenging
to deliver HDP as such inside the physiological system in a controlled way by conventional delivery
systems. Many HDPs are efficacious only at practically high molar-concentrations, which is not convincing
for the development of drug regimen due to their intrinsic detrimental effects. To avail the
efficacy of HDP in pulmonary diseases, it is essential to deliver an appropriate payload into the targeted
site of lungs. Inhalable HDP can be a potentially suitable alternative for various lung disorders
including tuberculosis, Cystic fibrosis, Pneumonia, Lung cancer, and others as they are active against
resistant microbes and cells and exhibit improved targeting with reduced adverse effects. In this review,
we give an overview of the pharmacological efficacy of HDP and deliberate strategies for designing
inhalable formulations for enhanced activity and issues related to their clinical implications.
In the presented study, we report development of a stable, scalable, and high-quality curcumin-loaded oil/water (o/w) nanoemulsion manufactured by concentration-mediated catastrophic phase inversion as a low energy nanoemulsification strategy. A design of experiments (DoE) was constructed to determine the effects of process parameters on the mechanical input required to facilitate the transition from the gel phase to the final o/w nanoemulsion and the long-term effects of the process parameters on product quality. A multiple linear regression (MLR) model was constructed to predict nanoemulsion diameter as a function of nanoemulsion processing parameters. The DoE and subsequent MLR model results showed that the manufacturing process with the lowest temperature (25 °C), highest titration rate (9 g/minute), and lowest stir rate (100 rpm) produced the highest quality nanoemulsion. Both scales of CUR-loaded nanoemulsions (100 g and 500 g) were comparable to the drug-free optimal formulation with 148.7 nm and 155.1 nm diameter, 0.22 and 0.25 PDI, and 96.29 ± 0.76% and 95.60 ± 0.88% drug loading for the 100 g and 500 g scales, respectively. Photostability assessments indicated modest loss of drug (<10%) upon UV exposure of 24 h, which is appropriate for intended transdermal applications, with expected reapplication of every 6–8 h.
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