Topical Drug Delivery Systems Based on Bacterial Nanocellulose: Accelerated Stability Testing.

Nuno H C S Silva,João P F Carvalho,Carla Vilela,Joana P Mota,Armando J D Silvestre,Tânia Santos De Almeida,Carmen S R Freire,Catarina Rosado

doi:10.3390/ijms21041262

Abstract

Bacterial nanocellulose (BNC) membranes have enormous potential as systems for topical drug delivery due to their intrinsic biocompatibility and three-dimensional nanoporous structure, which can house all kinds of active pharmaceutical ingredients (APIs). Thus, the present study investigated the long-term storage stability of BNC membranes loaded with both hydrophilic and lipophilic APIs, namely, caffeine, lidocaine, ibuprofen and diclofenac. The storage stability was evaluated under accelerated testing conditions at different temperatures and relative humidity (RH), i.e., 75% RH/40 °C, 60% RH/25 °C and 0% RH/40 °C. All systems were quite stable under these storage conditions with no significant structural and morphological changes or variations in the drug release profile. The only difference observed was in the moisture-uptake, which increased with RH due to the hydrophilic nature of BNC. Furthermore, the caffeine-loaded BNC membrane was selected for in vivo cutaneous compatibility studies, where patches were applied in the volar forearm of twenty volunteers for 24 h. The cutaneous responses were assessed by non-invasive measurements and the tests revealed good compatibility for caffeine-loaded BNC membranes. These results highlight the good storage stability of the API-loaded BNC membranes and their cutaneous compatibility, which confirms the real potential of these dermal delivery systems.

Highlights

Cellulose has been used throughout the years as a substrate for the design of functional blends, composites and hybrid materials in various fields of application [1,2,3]
bacterial nanocellulose (BNC) membranes were individually loaded with different active pharmaceutical ingredients (APIs), namely, caffeine, lidocaine, ibuprofen and diclofenac (Figure 1A)
Caffeine (1,3,7-trimethylxanthine) is the most widely consumed metabolic and central nervous system stimulant drug, it has a well-known effect on lipolytic activity in the adipocytes [33], and is soluble in water (21.7 mg mL−1 [34]) and ethanol; lidocaine (2-diethylamino-N-(2,6-dimethylphenyl) acetamide) is a hydrophilic local anesthetic drug with water solubility of 4.1 mg mL−1 [34]; ibuprofen (α-methyl-4-(isobutyl)phenylacetic acid) is a hydrophobic non-steroidal anti-inflammatory drug (NSAID) that is highly soluble in ethanol (538 mg mL−1 [36]) and poorly soluble in water (21 μg mL−1 [34]); and diclofenac (2-[(2,6-dichlorophenyl)amino]benzeneacetic acid) is a NSAID that is insoluble in ethanol and poorly soluble in water in the acidic form (2.37 μg mL−1 [34]) but with higher water solubility in the salt form (1.11 mg mL−1 [37])

Summary

Introduction

Cellulose has been used throughout the years as a substrate for the design of functional blends, composites and hybrid materials in various fields of application [1,2,3]. Bacterial exopolysaccharide (viz. BNC) has attracted a great deal of interest in several areas, ranging from nanocomposite materials [11,12,13] to food packaging films [14,15] and conductive membranes for fuel cells [7,16], but, its main application is still in the biomedical field [17,18,19,20]. Neat BNC membranes have already been combined with drugs and other bioactive compounds, such as lidocaine [22,23], ibuprofen [23], caffeine [24], diclofenac [25] and amoxicillin [26] in their most common forms or formulated as ionic liquids [27,28] for cutaneous drug delivery. There are examples of BNC-based nanocomposites being used for the cutaneous delivery of diclofenac [29] and BNC-based hybrid films for the cutaneous delivery of levofloxacin [30]

Objectives

Results

Conclusion