Hydrophobic Rifampicin Research Articles

Modifications of Ganoderma lucidum spores into digestive-tissue highly adherent porous carriers with selective affinity to hydrophilic or hydrophobic drugs

Ganoderma lucidum spores (GLSs) have been suggested to provide optimal structures for transporting orally bioavailable drugs. However, the double-layer wall and cavities of GLSs are naturally closed. This study aimed to modify GLSs into porous carriers by opening the layers and internal cavity with iturin A (IA) followed by potassium hydroxide (KOH) or hydrochloric acid (HCl). The (IA + KOH)- and (IA + HCl)-treated GLS carriers exhibited a high loading rate of 301.50 ± 2.33 and 268.18 ± 7.72 mg/g for the hydrophilic methylene blue (MB) and hydrophobic rifampicin (RF), respectively. The mechanisms underlying the modification involved the enhancement of the specific surface area with IA and the exposure of hydrophilic groups or hydrophobic groups of the GLSs with KOH or HCl. The sustained 48-h molecule-release profiles of the MB- and RF-loaded GLS carriers were best fitted using a first-order kinetics model in simulated gastric (or intestinal) fluid compared with other models. In mice, the designed GLS carriers had high adhesion capacities onto the mucosa of the digestive tract and long retention times (120 h), and even promoted the secretion of mucus and expression of several key intestinal barrier proteins. This study provided a new method to modify GLSs into oral carriers with selective drug affinity, high loading capacity, sustained drug release, and high adhesion to the digestive tract.

The influence of storage relative humidity on aerosolization of co-spray dried powders of hygroscopic kanamycin with the hydrophobic drug rifampicin

The purpose of this study was to investigate the influence of storage humidity on in vitro aerosolization and physicochemical properties of co-spray dried powders of kanamycin with rifampicin. The powders were stored for one-month in an open Petri dish at different relative humidities (RHs) (15%, 43%, and 75%) and 25 ± 2 °C. The in vitro aerosolization (fine particle fraction, FPF) of the powders was determined by a next generation impactor (NGI). The moisture content, particle morphology and crystallinity of the powders were determined by Karl Fischer titration, scanning electron microscopy, and X-ray powder diffractometry, respectively. At all RH, the FPF of hydrophobic rifampicin-only powder was unaffected but the FPF of hygroscopic kanamycin-only powder significantly decreased even at 43% RH. The kanamycin-only particles fused together, crystallized and formed hard cakes at 75% RH. The aerosolization of kanamycin and rifampicin in the combination powders remained unaffected at 15% and 43% RH, but aerosolization significantly decreased at 75% RH. Enrichment of the surface of the particles with hydrophobic rifampicin did not protect the combination powders from moisture uptake but it prevented particle agglomeration up to 43% RH. At 75% RH, the moisture uptake led to agglomeration of the particles of the combination powder particles and consequently an increase in aerodynamic diameter. Further studies are required to investigate how rifampicin enrichment prevents particle agglomeration, the possible mechanisms (e.g. particle interactions due to capillary forces or electrostatic forces) for the changes in the aerosolization and changes in surface composition during storage.

A bioactive implant in situ and long-term releases combined drugs for treatment of osteoarticular tuberculosis

Anti-tuberculosis chemotherapy with a long duration and adequate dosing is the mainstay for treatment of osteoarticular tuberculosis (TB). However, it is difficult for systemic administration to reach adequate local drug concentrations and achieve effective treatment. Herein, a hydroxyapatite (HA) scaffold implant combined with a drug-releasing system was designed to achieve in situ and long-term anti-TB drug release and highly efficient therapeutic activity in vitro and in vivo. The clinical anti-TB drugs hydrophilic isoniazid (INH) and hydrophobic rifampicin (RFP) were molecularly dispersed into polyvinyl alcohol (PVA) through immersion-curing techniques and were steadily adhered onto the surfaces of HA scaffolds (HA-drug@PVA). The HA-drug@PVA scaffolds showed a long-term, sustained drug release profile and killed proliferating Mycobacterium in vitro. In vivo experimental results revealed that the HA-drug@PVA scaffolds provided over 10- and 100-fold higher concentrations in muscles and bones, respectively, as well as a much lower concentration (<0.025) in blood. Furthermore, the HA-drug@PVA scaffold implanted in an osteoarticular TB rabbit model showed obvious bone regeneration and fusion due to the inhibition of TB-associated inflammatory changes. The excellent therapeutic effects indicate that in situ implant materials combined with a long-term drug release system are promising for the treatment of osteoarticular TB and other osteoarticular infections.

Preparation, characterization, drug release and computational modelling studies of antibiotics loaded amorphous chitin nanoparticles

We present a computational investigation of binding affinity of different types of drugs with chitin nanocarriers. Understanding the chitn polymer-drug interaction is important to design and optimize the chitin based drug delivery systems. The binding affinity of three different types of anti-bacterial drugs Ethionamide (ETA) Methacycline (MET) and Rifampicin (RIF) with amorphous chitin nanoparticles (AC-NPs) were studied by integrating computational and experimental techniques. The binding energies (BE) of hydrophobic ETA, hydrophilic MET and hydrophobic RIF were −7.3kcal/mol, −5.1kcal/mol and −8.1kcal/mol respectively, with respect to AC-NPs, using molecular docking studies. This theoretical result was in good correlation with the experimental studies of AC-drug loading and drug entrapment efficiencies of MET (3.5±0.1 and 25± 2%), ETA (5.6±0.02 and 45±4%) and RIF (8.9±0.20 and 53±5%) drugs respectively. Stability studies of the drug encapsulated nanoparticles showed stable values of size, zeta and polydispersity index at 6°C temperature. The correlation between computational BE and experimental drug entrapment efficiencies of RIF, ETA and MET drugs with four AC-NPs strands were 0.999 respectively, while that of the drug loading efficiencies were 0.854 respectively. Further, the molecular docking results predict the atomic level details derived from the electrostatic, hydrogen bonding and hydrophobic interactions of the drug and nanoparticle for its encapsulation and loading in the chitin-based host-guest nanosystems. The present results thus revealed the drug loading and drug delivery insights and has the potential of reducing the time and cost of processing new antibiotic drug delivery nanosystem optimization, development and discovery.