Investigations of amphiphilic butylglyceryl‐functionalized dextran nanoparticles for topical delivery

Abstract

Toward the development of colloidal systems that can enhance transdermal permeation of hydrophilic actives, a material combining the non‐toxic of dextran with alkylglycerols permeation enhancing property has been designed. To this purpose, a range of amphiphilic butylglyceryl dextrans (DEX‐OX4) was synthesized via modification with n‐butylglycidyl ether with a degree of functionalization in the range 6.3%–35.7%. A reduced viscosity and an increased molecular weight of DEX‐OX4 were recorded when compared to the starting material. DEX‐OX4 was formulated into nanocarriers and loaded with α‐arbutin prior to characterization—the nanoparticles (180–220 nm size) were found to be close‐to‐spherical, stable at pH 5 and 7, with a loading capacity of 11.7%. Slower release of α‐arbutin from the nanoparticles was demonstrated when tested in acidic media. Lack of toxicity at application‐relevant concentrations and increased permeation were demonstrated by nanoparticles in vitro results against immortalized skin human keratinocytes cells (HaCaT).

Amphiphilic Alkylated Pectin Hydrogels for Enhanced Topical Delivery of Fusidic Acid: Formulation and In Vitro Investigation

“…When compared to native pectin hydrogels, the penetration and flux of fusidic acid across the Strat-M ® membrane after 8 h was 1.5 times greater when formulated with amphiphilic alkylated pectin hydrogels. This is in accordance with our prior findings that reported higher drug permeation across skin models when formulated with amphiphilic polysaccharides [19,28]. Even though the exact mechanisms are obscure, it is possible that the amphiphilic alkylated pectin loosens the tight lipid packing and lowers barrier resistance, allowing more solute to pass through the skin [52].…”

“…The absorption band at 1764 cm −1 is caused by the carbonyl group of the methyl ester (-COOCH3) and unionized carboxylic acid (-COOH), whereas the band at 1648 cm −1 is caused by the asymmetric stretching band of the carboxylate ion (COO-) [26]. Due to the formation of more linear ether (COC) links and the addition of more methyl groups, alkylation with GTBE increased the strength of the ether band (1149-1020 cm −1 ) as well as the -CH vibration bands (2921-2884 cm −1 ) [27][28][29]. The synthesis was also validated using NMR spectroscopy.…”

Hydrophobically Grafted Pullulan Nanocarriers for Percutaneous Delivery: Preparation and Preliminary In Vitro Characterisation

“…Lower hydrogen-bonded H 2 O molecules in BMO-PUL derivatives may be attributed to enhanced hydrophobicity after the modification, which ultimately limits them from retaining additional moisture. This is in line with earlier studies on the alkylation of polysaccharides (dextran and pectin) with short-chain alkylglycerols [ 31 , 38 ]. BMO-PUL showed increased thermal stability compared to the native, as evidenced by the DTG peak corresponding to the decomposition of the BMO-PUL derivatives that surfaced at a greater temperature.…”

“…From the data ( Figure 13 ), an increase in conc. did not initiate a significant reduction in cell viability (with more than 85% cell viability over the whole concentration range) following incubation for 24 h. This is in line with earlier findings that reported the lack of toxicity for nanoparticles formulated from hydrophobically grafted polysaccharides with short-chain alkylglycerols in various drug delivery applications [ 21 , 31 ].…”

“…One approach to introduce a degree of hydrophobic character to polysaccharides is alkylation, which results in modified physicochemical properties affecting the membrane permeation ability [ 29 ] and ultimately the bioactivity of the whole macromolecule [ 21 , 30 , 31 ]. Different reagents, including epoxide derivatives such as 2-(butoxymethyl)oxirane, can be used to add alkyl groups to hydrophilic polysaccharides.…”