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Poloxamer 407-Based Thermosensitive Emulgel as a Novel Formulation Providing a Controlled Release of Oil-Soluble Pharmaceuticals-Ibuprofen Case Study.

ABSTRACT: This article covers the design and evaluation of a novel drug vehicle: a thermosensitive, injectable, high-oil-content (50% w/w) emulgel providing a controlled release of lipophilic pharmaceuticals. Different vegetable (castor, canola, olive, peanut, grapeseed, linseed), mineral (paraffin) and semisynthetic (isopropyl myristate, oleic acid) oils were screened for ibuprofen (IBU) solubility and for their capacity for high-shear emulsification in a 17% (w/w) aqueous solution of poloxamer 407. Chosen emulgels were subject to a rheological evaluation, a syringeability test (TA.XT texture analyser; 2 mL syringe; 18 G, 20 G and 22 G needles) and a drug release study (48 h; cellulose membrane; 0.05 mol/L phosphate buffer at pH 7.4). Castor oil turned out to be an optimal component for IBU incorporation. Blank and drug-loaded castor oil emulgels were susceptible to administration via a syringe and needle, with the absolute injection force not exceeding 3 kg (29.4 N). The drug release test revealed dose-dependent, quasi-linear kinetics, with up to 44 h of controlled, steady, linear release. The results indicate the significant potential of high-oil-content, oil-in-water thermosensitive emulgel formulations as vehicles for the controlled release of lipophilic APIs.

SUBMITTER: Grela KP

PROVIDER: S-EPMC8658182 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The current study aimed to develop poloxamer 407 (P407) gel for transungual delivery of antifungal hydrophobic drugs with sufficient gel strength and drug loading. Gel strength and drug loading of P407 gel was improved by use of functional additives. Hydration enhancement effect was used to select optimum nail penetration enhancer. Face-centered central composite design (FCCCD) was used to observe the effect of the selected penetration enhancer (thioglycolic acid (TGA)) and cosolvent (ethanol) on gelation behavior to develop formulation with enough loading of hydrophobic drug, i.e., terbinafine HCl (TBN), and its permeation across the nail plate without compromising on gel strength. It was observed that increasing concentration of P407 and TGA significantly reduced gelation temperature and enhanced the gel strength of P407 gel and can be used to improve P407 gel strength. Under the scanning electron microscope, the significant effect of TGA as an ungual penetration enhancer was observed on the morphology of the nail plate. Optimized P407 gel prepared with modified cold method showed a gelation temperature of 8.7 ± 0.16 °C, gel strength of 122 ± 7.5 s and drug loading of 1.2% w/w, which was four times more than the drug loading in the gels prepared with conventional cold method. Rheological behavior was pseudoplastic with 47.75 ± 3.48% of gel erosion after 12 washings and 67.21 ± 2.16% of drug release after 12 h. A cumulative amount of TBN permeated from P407 gel with and without PE after 24 h was 27.30 ± 4.18 and 16.69 ± 2.31 µg/cm2, respectively. Thioglycolic acid can be used as a nail penetration enhancer without the chemical modification or addition of extra additives while retaining the gel strength. Water miscible cosolvents with moderate evaporability such as ethanol, can be incorporated to P407 gel by minor modification in method of preparation to load the required dose of hydrophobic drugs. Developed P407 gel formulation with sufficient gel strength and drug loading will be a promising carrier for transungual delivery of hydrophobic antifungal agents.

Project description:ObjectiveNerve growth factor (NGF) has potential in spinal cord injury (SCI) therapy, but limited by the poor physicochemical stability and low ability to cross the blood spinal cord barrier. Novel heparin-poloxamer (HP) thermo-sensitive hydrogel was constructed to enhance the NGF regeneration on SCI.MethodNGF-HP thermo-sensitive hydrogel was prepared and related characteristics including gelation temperature, rheological behavior and micromorphology were measured. Local NGF delivery to the injured spinal cord was achieved by in situ injection in the injured space. The cellular uptake of NGF-HP hydrogel was evaluated with PC12 cells in vitro. Pathologic characteristics and neuron regeneration effects on the SCI rats were studied to evaluate the enhanced therapy of NGF-HP hydrogel. Endoplasmic reticulum (ER) stress-induced apoptosis was analyzed to explore the related mechanism in SCI regeneration.ResultsNGF-HP hydrogel showed good morphology and stable bioactivity of NGF in vitro. NGF-HP hydrogel combined treatment significantly enhanced the efficiency of NGF cellular uptake (P<0.05) without obvious cytotoxicity. Significant improvements in both neuron functions and tissue morphology on the SCI rats were observed in NGF-HP hydrogel group. Compared with free HP hydrogel and NGF treatment groups, NGF-HP hydrogel group showed significant inhibition on the formation of glial scars in the extreme crushed rat SCI model. The neuroprotective effects of NGF-HP were related to the inhibition of chronic ER stress-induced apoptosis.ConclusionsHP hydrogel combined with orthotopic injection technique might be an effective method to deliver NGF into the injured site, which will provide an effective strategy for SCI regeneration.Statement of significanceSpinal cord injury (SCI) is a devastating condition that can lead to sudden loss of sensory and autonomic function. Current treatment includes decompression surgery, injury stabilization, secondary complications prevention and rehabilitation. However, neurological recovery is limited. Nerve growth factor (NGF) has potential in SCI therapy, but limited by the poor physicochemical stability and low ability to cross the blood spinal cord barrier. Hydrogels have good affinity and compatibility to biological tissue. In this study, we developed a novel heparin-poloxamer (HP) thermo-sensitive hydrogel to enhance the spinal cord regeneration of NGF. From SCI rat experiment, HP hydrogel combined with orthotopic injection technique showed best neuroprotective effects among experimental groups. This novel combined technique will provide an effective strategy for SCI regeneration.

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Poloxamer 407-Based Thermosensitive Emulgel as a Novel Formulation Providing a Controlled Release of Oil-Soluble Pharmaceuticals-Ibuprofen Case Study.

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