Assessment of the efficacy of drug transdermal delivery by electro-phonophoresis in treating tuberculous lymphadenitis

Abstract

Electro-phonophoresis (EP) has been used in various clinical fields. The objective of present study is to evaluate the skin permeability of isoniazid (INH) and rifampicin (RIF) in patients with tuberculous lymphadenitis with the aid of EP to validate the clinical applications of this transdermal delivery system for the treatment of superficial extrapulmonary tuberculosis. INH and RIF solutions were delivered transdermally, with or without EP, in the surrounding tissue of the lesion for 0.5 h. Local pyogenic fluids or necrotic tissue samples from the infection sites in patients were collected at 1 h after dosing. Drug concentrations in samples were evaluated by high performance liquid chromatography. The median INH and RIF intra-lesional concentrations were 0.365 (interquartile range [IQR] 0.185-1.775) mg/mL and 1.231 (IQR 0.304-1.836) mg/mL in oral group; 2.964 ) mg/mL and 2.646 (IQR 1.211-3.753) mg/mL in INH-and RIF-transdermal plus EP group. Drug concentrations in the local sites of patients receiving INH or RIF through EP transdermal delivery were statistically higher than those observed in patients only taking INH and RIF orally. However, this enhancement was not observed in the transdermal delivery of INH or RIF without EP in contrast to the oral administrations of drugs. EP can effectively enhance the skin permeability of INH and RIF in patients with tuberculous lymphadenitis. The increase in drug concentrations in the lesions could help eradication of the germs; shorten the treatment course and increase the cure rate of patients with tuberculous lymphadenitis.

Transdermal delivery of isoniazid and rifampin in guinea pigs by electro-phonophoresis

“…However, these results are a little different from that of our previous study, in which we examined whether EP can effectively increase the penetration of the INH and RIF through skin in tuberculous lymphadenitis patients and verified that application of EP significantly enhances both INH and RIF penetration through skin (Chen et al, 2016). Because of the difficulty of obtaining the pyogenic fluids, the pharmacokinetic studies of the change of drug concentrations in pyogenic fluids over an extended period of time and the optimal ultrasonic intensity and dosage were not addressed in previous study.…”

<p>Novel Approach for Transdermal Delivery of Rifampicin to Induce Synergistic Antimycobacterial Effects Against Cutaneous and Systemic Tuberculosis Using a Cationic Nanoemulsion Gel</p>

“…These values were significantly (p ˂ 0.05) higher than previously reported, and were high enough to kill skin cells and promote RIF values in the circulation substantially higher than the minimum inhibitory concentration (0.25 µg/mL) of RIF. 41 These results showed that RIF-loaded nanoemulsions may be promising formulations for transdermal delivery of RIF.…”

“…Drug precipitation from the o/w nanoemulsion in the skin strata was not of concern because RIF is lipophilic. 41 In contrast, isoniazid, which is hydrophilic, has been used for sustained topical delivery, which may result from precipitation in lipophilic skin regions. 41 The desirability function was used to validate the optimization parameters and to specify constraints for responses.…”

“…47 Transdermal delivery of RIF using electro-phonophoresis was previously shown to slightly improve the transport of RIF across guinea pig skin. 41 This showed that transdermal delivery of RIF to treat superficial tuberculosis may be a promising strategy. 41 Therefore, nanoemulsion gel-based nanocarriers could be promising formulations for the treatment of local and systemic tubercular infections.…”

“…41 This showed that transdermal delivery of RIF to treat superficial tuberculosis may be a promising strategy. 41 Therefore, nanoemulsion gel-based nanocarriers could be promising formulations for the treatment of local and systemic tubercular infections.…”