At present, a variety of chemical drugs are combined with nano-carriers to make lung-inhaled nano-preparations, and have achieved good results, such as anti-tuberculosis drugs, itraconazole, terbutaline sulfate, ciprofloxacin, curcumin and Camptothecin.
Anti-tuberculosis drugs
Polylactic acid glycolic acid (PLGA) has good biodegradability and biocompatibility, and is widely used as a drug carrier. The pulmonary tuberculosis drugs rifampicin, isoniazid, and pyrazinamide are prepared by the double emulsion/solvent volatilization method to prepare PLGA nanoparticles for pulmonary administration. The particle size is 180-300m, and the encapsulation rate is 50%- 70%. Rifampicin PLGA nanoparticles were prepared by a double emulsion method, and the nanoparticles were dissolved in an alginic acid solution and spray-dried to obtain nano-mixed particles with an average particle size of 2 μm, which was suitable for pulmonary administration.
Itraconazole
Itraconazole is a triazole class of high-efficiency broad-spectrum antifungal drugs, which can combine with fungal cytochrome P450 isoenzymes to inhibit the synthesis of ergosterol. Itraconazole is effective against Dermatophytes, Candida, Cryptococcus neoformans, Pityrosporum, Aspergillus, Histoplasma, Paracoccus brasiliensis, Sporothrix Schenckii, Color fungi, Cladosporium It is effective for infections such as mold and dermatitis blastomycetes.
Itraconazole nanoparticles were prepared by freeze-spray drying. The prescription was itraconazole, polysorbate 80: poloxamer 407 (1: 0.75: 0.75). After a single spray administration, the drug was in the lungs. The highest concentration of the drug is 13. 4μg/g, the half-life is 5.5h, and the continuous administration is 12 days. The drug in the atomized administration group has a higher concentration in the lungs, which is more than 10 times that of the oral administration group.
Terbutaline Sulfate
Terbutaline sulfate tablets are indicated as anti-asthmatic drugs. It is suitable for bronchial asthma, chronic bronchitis, emphysema and other lung diseases accompanied by bronchospasm.
Loading high-purity hydrophilic and easily ionized drugs with human hydrophobic microspheres can reduce the internal polymerization of the nanoparticles and improve the aerodynamic properties of the powder. Terbutaline sulfate hydrophobic nanoparticles were prepared by emulsification and spray drying methods, in which Span 60 and DPPC were used as dispersants, and the aerodynamic particle size of the multi-nanoparticle polymer particles obtained was 3.93pm, the effective site deposition amount Up to 46.5%, meeting the requirements of pulmonary drug delivery. The terbutaline sulfate liposome was prepared, and its in vitro release conformed to the Higuchi equation. After intratracheal instillation of rats, the sustained release of the drug was up to 12 hours, and the sustained-release effect was very significant.
Ciprofloxacin
Ciprofloxacin is a synthetic third-generation quinolone antibacterial drug with broad-spectrum antibacterial activity and good bactericidal effect. The antibacterial activity against almost all bacteria is 2 to 4 times stronger than norfloxacin and enoxacin. Enterobacter, Pseudomonas aeruginosa, Haemophilus influenzae, Neisseria gonorrhoeae, Streptococcus, Legionella, and Staphylococcus aureus have antibacterial effects.
Adding an effervescent agent to the prescription can produce a rapid drug release effect, in order to quickly exert the drug effect and improve the drug release. The poly-n-butyl cyanoacrylate nanoparticles of ciprofloxacin are prepared, mixed with lactose, and sodium carbonate and citric acid of different concentrations are added as effervescent agents, and the proportion of inhalable particles (FPF) is 46.47%. The release rate of ciprofloxacin in the effervescent group was 56%, which was significantly better than that of the no effervescent group.
Curcumin
Curcumin is a natural compound with good anti-inflammatory and anti-cancer properties. In order to overcome the problems of poor solubility, instability, low absorption rate, and poor stability of the drug, the drug can be prepared into liposomes for administration in the lungs. Using curcumin as a model drug, liposomes were first prepared by a thin film dispersion method to obtain liposomes with a particle size of 30 nm, uniform distribution, an encapsulation efficiency of 89.1%, and good stability. The spray drying method is used to prepare liposome dry powder inhalants with lactose as a carrier. The powder has good fluidity and a high deposition rate of effective parts in vitro, which can reach 46.71%. Compared with curcumin suspension, its preparation into liposome powder aerosol for administration has obvious advantages in the treatment of acute lung injury.
Camptothecin
Camptothecin is a plant anti-cancer drug, which has good curative effect on gastrointestinal and head and neck cancer. Its derivatives also have obvious curative effect on liver cancer and head and neck cancer, and have fewer side effects. Use 9-nitrocamptothecin liposome to treat mouse subcutaneous xenograft lung metastasis model of human tumor. The liposome has a significant effect in aerosol inhalation, but it is ineffective in oral administration. Therefore, it can eliminate mouse swallowing lipids during aerosol inhalation.
It is possible for the body to produce drug effects after absorption in the digestive tract. The liposome intramuscular injection is also effective for tumors, but its curative effect is significantly lower than that of the same dose atomized inhalation group. Inhalation of 9-nitrocamptothecin liposomes in the treatment of mouse melanoma and osteosarcoma lung metastasis models, each inhalation for 1 hour (153mg/kg), 5 times a week, after 3 weeks of continuous treatment, the Compared with the untreated control group, the number of tumors was significantly reduced, and the weight of lung tumors also decreased. Therefore, the pulmonary administration of 9-nitrocamptothecin liposomes has a promising prospect in the treatment of lung tumors.
CD Bioparticles is an established drug delivery company which provides customized solutions for developing and producing new, biocompatible drug delivery systems.