Allergies arise from an immune system response to a foreign body. Allergic reaction is common and is characterized by the release of histamine, cytokines, and other mediators that may induce mast-cell degranulation. Antihistamines provide symptomatic relief to allergic conditions. Anti-histaminic drugs include loratadine, cetirizine, meclizine, bromopheniramine [1].
Tricyclic piperidine derivative loratadine (LoR) is a member of the second generation of H1-antihistamines and is used to treat urticaria, angioedema, and other allergic skin symptoms. It prevents the symptoms associated with histamines on gastrointestinal smooth muscle, bronchial smooth muscle, capillaries including increased capillary permeability, vasodilation. It is administrated by oral route for the treatment of skin conditions categorized by localized allergic reaction [2]. The cutaneous route should be a better option for drug delivery because the oral route has a limited bioavailability and causes side effects. Because of its high lipophilicity (log p = 5.2) and low molecular weight (382.88 Da), LoR is an excellent option for cutaneous distribution. However, LoR's limited topical applicability is due to its low water solubility [3].
Nanosponges (NS) are a new class of nanoparticles (NPs) with a small mesh-like 3D structure, smaller than 100 nm, with wide nanometric cavities that encapsulate a wide range of hydrophilic and lipophilic substances. Because of the inner hydrophobic cavities and external hydrophilic branching, they can easily load the particles [4]. The backbone is represented by a long chain of polyesters. The polymers are bound together by small molecules named as cross-linkers. NS can be used to carry water insoluble drugs which mainly belongs to BCS class II and IV [5]. NS are non-irritating, non-mutagenic, non-toxic, non-allergenic and biodegradable which are advantageous compared to other nanoparticulate systems; also, their release is predictable, are stable up to 130 ℃ and at pH of about 1–11; they can entrap a wide variety of ingredients, protecting the drug from degradation, and offering reduced side effects; they have overall better physical, chemical and thermal stability; they allow extended release for up to 12 h; eventually, these preparations are cost effective [6].
Hydrogels are cross-linked water-soluble polymers with 3D structure. If the molecular entanglement and/or secondary forces like hydrogen bond, ionic bond are responsible for the formation of linkage, then the hydrogel can be termed as reversible or physical gels. The hydrogels can be prepared by various physical forms like microparticles, slab, coating, films. The loading of the drug in the matrix and the drug release rate also depends upon the porosity of the gel matrix [7, 8].
The novelty of NS hydrogel lies in its unique properties as a highly porous material with nanoscale dimensions that can absorb and retain large quantities of substances such as drugs, toxins, or heavy metals. It can also release these substances in a controlled manner, making it a promising candidate for drug delivery, wound healing, and environmental remediation applications. Additionally, the biocompatibility and biodegradability of NS hydrogels make them a safer and more sustainable alternative to other materials currently used in similar applications.
Pharmaceutical formulations including NPs, NS, liposomes are prepared by employing specific processes that consider a number of different variables and aspects. These independent factors interact to generate efficacy, utility, stability, and safety. As a result, in order to get the intended result, it is frequently required to adjust the formulation processing settings. The quantitative methods intricacy in building the design represents the real link between the contributing elements and reactions, and the detailed for one property isn't necessarily the best for the others [9]. It is common knowledge that traditional experimentation takes a significant amount of time and effort, particularly when evaluating complicated systems.
A full factorial experiment includes every possible level for every component. There are total of 2k experiments in order to analyse k components at 2 levels. The 2k full factorial design is quite useful in the early stages of experimental work, particularly in cases when there are less than or equal to 4 process parameters, design parameters, or other components [10]. For factors at 2-levels, it assumes that the response is approximately linear over the range of the chosen factor setting. There are merely two variables in the first design of the 2k series, A and B, which will each be investigated twice.
The current study used the emulsion solvent evaporation approach to create LoR-loaded NS (LoR-NS) in gel. To optimise a 32 Full Factorial Design (FFD), the concentration of the LoR:EC ratio and the stirring rate were changed. The chosen formula was also examined for cutaneous irritation and histopathology.