Isoniazid-gelatin conjugate microparticles containing rifampicin for the treatment of tuberculosis.
OBJECTIVE
In this work, a new polymeric microparticle system based on gelatin covalently bound to isoniazid (ISN) and containing rifampicin (RFP) was prepared by spray-drying technique. Microparticle aptitude to nebulisation and their capability of interacting with A549, alveolar basal epithelial cells, were evaluated in vitro.


METHODS
Microparticles were obtained by spray drying, and their morphology, size, zeta potential, thermotropic behaviour and nebulisation ability were evaluated.


RESULTS
Microparticles were positively charged with a mean size of 4.88 ± 0.3 μm. Microspheres were able to incorporate both RFP and ISN: encapsulation efficiency was 51 ± 6% and 22 ± 1%, respectively. X-ray diffraction study showed a new extensive and flattened diffraction peak providing evidence that the drugs were dispersed into the microparticles. Differential scanning calorimetry analysis confirmed effective interactions between gelatin and drug molecules by the presence of new transition peaks. Fifty-nine per cent of used microparticles were aerosolised. In-vitro toxicity studies on A549 alveolar basal epithelial cells showed that microparticles decreased cytotoxicity in comparison with the RFP solution. Laser scanning confocal microscopy observation confirmed that fluorescent probes delivered by microparticles are efficiently internalised in A549 cells.


CONCLUSIONS
Overall, microparticles based on gelatin covalently bound to ISN and containing RFP showed a promising behaviour for pulmonary drug delivery.
Department Scienze della Vita e dell'Ambiente, Sezione Scienze del Farmaco, Cagliari, Italy.
Maria L
ML
Manca
Roberta
R
Cassano
Donatella
D
Valenti
Sonia
S
Trombino
Teresa
T
Ferrarelli
Nevio
N
Picci
Anna M
AM
Fadda
Maria
M
Manconi
D000280:Administration, Inhalation; D000336:Aerosols; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D002460:Cell Line; D003890:Desiccation; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005780:Gelatin / Q000737:chemistry; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008863:Microspheres; D010316:Particle Size; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism; D012293:Rifampin / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D014376:Tuberculosis / Q000188:drug therapy*
D000336:Aerosols; D000995:Antitubercular Agents; D004337:Drug Carriers; D005780:Gelatin; D007538:Isoniazid; D012293:Rifampin
A549 cells; antimicobacterial drugs; microparticles; pulmonary drug delivery; toxicity studies