Formulation and Release Behavior of Doxycycline–Alginate Hydrogel Microparticles Embedded into Pluronic F127 Thermogels as a Potential New Vehicle for Doxycycline Intradermal Sustained Delivery

Abstract

Abstract. The aim of this work was the formulation and characterization of alginate (ALG)-doxycycline (DOX) hydrogel microparticles (MPs) embedded into Pluronic F127 thermogel for DOX intradermal sustained delivery. ALG-DOX MPs were formed by adding a solution of the drug into a 1.5% polymer solution while stirring. The MPs were cross-linked by dispersion into a 1.2% CaCl 2 solution. Free MPs were characterized in terms of size, drug content, and release behavior by HPLC and UV-vis. DOX and hydrogel MPs were embedded into PF127, PF127-HPMC, and PF127-Methocel thermogels. The thermogels were characterized in terms of gelling time, morphology, and release behavior. A target release period of 4-7 days was considered optimal. The hydrogel MPs were about 20 µm in size with 90% of the population <59 µm. Drug content was about 35% (w/w). DOX released rapidly from the MPs, 90% within 2 days. An expected faster release was observed for free DOX from the thermogels with 80-90% of drug released after 3.5-4 h even in the presence of 1% HPMC or Methocel. The release was sustained after embedding the MPs into PF127 and PF127-HPMC thermogels. In particular, the PF127-HPMC thermogel showed an almost linear release, reaching 80% after 3 days and 90% up to 6 days. Although a further characterization and formulation assessment is required to optimize MP characteristics, ALG/DOX-loaded hydrogel MPs, when embedded into a PF127-HPMC thermogel, show a potential for achieving a 7-day sustained release formulation for DOX intradermal delivery.

Effects of Antibiotic Physicochemical Properties on Their Release Kinetics from Biodegradable Polymer Microparticles

“…In the 10 wt% group, colistin loaded more efficiently than doxycycline, while in the 20 wt% group, colistin loaded more efficiently than vancomycin. Doxycycline, a tetracycline antibiotic, and vancomycin, a glycopeptide antibiotic, both had high entrapment efficiencies and are positively charged at pH 6.4, but due to the multitude of pKa values spanning a large pH range, both antibiotics also contain a negative charge that may have lowered its loading efficiency compared to colistin [32,33]. Negative-negative antibiotic-polymer charge interactions can promote the expulsion of cefazolin from the MPs, while favorable positive-negative interactions enhance the retention of zwitterionic and positively charged antibiotics.…”

Stable integration of an optimized inducible promoter system enables spatiotemporal control of gene expression throughout avian development

“…Their lower jaws were then harvested and either injected along the right side with minocycline microspheres or with dox gel (Pluronic F-127). Pluronic F-127 is a liquid at low temperatures (4 °C) but solidifies at higher temperatures (37 °C) and has been used for delivering drugs to different tissues (Harris et al, 2004;Giovagnoli et al, 2010). After 12 hours of treatment with either minocycline microspheres or with dox gel, we observe RFP expression localized on the right side of the jaw, which becomes more elevated by 24 hours (Fig.…”

Inkjet‐Printed Alginate Microspheres as Additional Drug Carriers for Injectable Hydrogels

“…This is in comparison to common procedures, where the fabrication of drug carrying carriers and the matrix polymer were prepared separately in multiple steps. 13,16,23 Lutrol F127 was selected as the drug carrier for injectable applications due to its reversible sol-gel transition behavior and ability to incorporate both hydrophilic and hydrophobic substances that are insoluble in aqueous solution. It is well documented in the literature that both micellization and gelation depend on different factors, namely, temperature and polymer concentration.…”