A Critical Review on Emerging Trends in Dry Powder Inhaler Formulation for the Treatment of

Bronchiolitis, on the other hand, is the inflammation of the smaller airways and bronchioles in the lungs. In addition, mannitol also has the ability to stabilize the amorphous form of ITZ in the formulation, which may contribute to the better aerosol performance of the formulation. This can be attributed to the strength and elasticity of the bridges between the drug particles added by the polymer stabilizer.

The sustained release properties of the formulation were due to the slow release of the drug from the controlled release polymer, PLA, entrapping the drug within the polymer matrix [40]. It was reported that the introduction of leucine into the formulation would further improve the aerosolization performance of the dry powder formulation. The authors further concluded that the aerosolization performance of the developed microparticle formulation was significantly improved, which may be due to the presence of leucine.

The higher dissolution rate of ITZ-SA may be due to the higher disorder in the triazolone ring of ITZ-SA, which may be reflected through its lower melting point. This is consistent with the improved aerodynamic performance of the formulation in the study by Duret et al. This may be due to the fact that chitosan increased the bio-adhesion of the particles.

This penetration of the liposomal aerosol to the periphery of the lungs can lead to rapid availability of drugs [73]. This high EE was due to the low water solubility and high affinity of the lipophilic ITZ for Precirol ATO 5 and oleic acid. This may be due to the large surface area provided by the NLC in addition to the short diffusion distance for ITZ from the lipid matrix in the dissolution medium as the drug is enriched in the outer region of the NLC.

Thus, a study had evaluated the effect of autoclaving on the stability of ITZ-loaded NLC formulation with the same excipients as described in the previous study [77]. A gamma camera image of a hawk after inhalation of the developed ITZ-NLC formulation from (a) lateral and (b) dorsal side [79]. However, the lipid was important in the dissolution of poorly water-soluble AmB in water.

While the hydrophilic shell is essential for the in vivo behavior of the polymeric micelles. This rapid release may be due to the adsorption of drug molecules at the outer regions of the polymeric micelles. The variation in the particle sizes can be caused by the aggregation of the particles.

The release pattern may be due to initial diffusion followed by polymer diffusion and degradation.

Figure 2. Pathophysiology of pulmonary aspergillosis.

Expert Opinion

Different approaches based on nanocarriers via intravenous administration for the treatment of PAS are summarized in Table 5. To prepare CMC-coated ITZ-loaded liposomes and to study the physicochemical properties, in vitro antifungal activities, safety evaluation, pharmacokinetics and tissue distribution of liposomes. CHOL, CMC ITZ Thin film delivery C. ITZ-CMC liposomes showed higher mean retention time and AUC than commercially available.

To develop an alternative liposomal formulation for AmB using the simpler SCF-CO2 method and to examine the effects of various factors. To prepare LNs that can entrap poorly water-soluble drug, AmB with high drug EE in them. 293 cells, Sprague-Dawley rats, Sprague-Dawley rat RBC,C. PEG-LN AmB showed higher circulating half-life and higher AUC0-24h than Fungizone® and AmBisome®.

To develop an IV formulation of ITZ using lipid nanoparticles based on binary mixture of liquid and solid lipids. -incorporated lipid nanoparticles with modulated release property using a binary mixture core of solid and liquid lipid for oral and parenteral administration. To develop a lung-specific delivery system of AmB with a high pulmonary distribution and a low nephrotoxicity.

-DCH has a higher drug delivery to the lungs and 15 times lower drug concentration in the kidneys compared to liposomal AmB formulation. -α-tocopheryl polyethylene glycol 1000 succinate-b-poly. ε-caprolactone-ran-glycolide) nanoparticles and to evaluate their in vitro and in vivo antifungal activity. nanoparticles PLGA, TPGS 1000 AmB Modified. -NP showed about 50% lower of log CFU/gram C. albicans in the infected mice than the free AmB. AmB-NP showed 50% higher survival rate in the infected mice than the free AmB.

To evaluate the fungistatic and fungicidal effects of AmB-loaded D-α-tocopheryl polyethylene glycol 1000 succinate-b-poly. ε-caprolactone-ran-glycolide) nanoparticles for the treatment of lung fungal infections. No detectable lesions and edema found and lower fungal burden after treatment with AmB-NP. AmB-NP showed a 40% higher survival rate in the infected mice than the PLGA-AmB.

Table 5. Nanocarriers for intravenous formulation against pulmonary aspergillosis.

Safety Concerns of Dry Powder Inhaler Formulations against Pulmonary Aspergillosis

The lower hematotoxicity of the LN formulation of AmB to RBCs of Sprague-Dawley rats suggested a decrease in direct contact of AmB with RBCs due to the lipid matrix of LN and slower drug release due to the interaction of AmB with phospholipids and cholesterol [98]. Regarding the safety of the polymeric drug delivery system, some researchers have performed toxicity evaluations in different cell lines or animal models. This indicated that AmB-PMA was superior to Fungizone® as the lytic and cytotoxic effects of deoxycholic acid of Fungizone® could be prevented [92].

Interestingly, the unloaded nanoparticles showed no hemolytic ability to red blood cells when the concentration was below 1.0 mg/ml. Moreover, an in vivo toxicity test was performed on mice receiving the treatment intravenously, and the results showed that the lower concentration of AmB-NP than that of free AmB resulted in 50% mortality in the mice which again proved that AmB -NP lower toxicity and higher efficacy [102]. In a study by Amaral et al., although 6 mg/kg every 3 days of Nano-D-AmB was expected to cause severe toxicity to the animals, since the recommended dose of AmB is 1 mg/kg/day, kidney - and hepatic biochemical parameters including blood urea nitrogen, creatinine, glutamic oxaloacetic transaminase and glutamic pyruvate transaminase showed normal after the administration of Nano-D-AmB.

The lack of toxicity of Nano-D-AmB is most likely due to the site-targeting effect offered by DMSA and the low circulation of pure AmB due to the sustained release properties of Nano-D-AmB. In addition, no genotoxicity or cytotoxicity was detected in bone marrow cells after performing the micronucleus test on Nano-D-AmB. The absence of toxicity may be due to the sustained release properties and low accumulation of AmB due to the complexation of polymeric nanoparticles [105].

Nano-D-AmB was further tested by another researcher to evaluate the in vitro biosafety, where the results showed that Nano-D-AmB induced a lower level of hemolysis even at lower concentration compared to Anforicin B®, another commercial AmB product. in Brazil. Apart from that, Nano-D-AmB did not show significant viability of peritoneal macrophages, which also proves the safety of the formulation, whereas the viability of peritoneal macrophages was reduced after incubation with Anforicin B®[106]. This may be due to the sustained release of ITZ from Nano-D-ITZ, lower concentration injected and less dosing rate [107].

Based on the reviewed literature, it was demonstrated that the antifungal formulations using lipid-based and polymeric nanocarriers have improved safety profiles compared to commercially available antifungal formulations. This suggests the feasibility of the investigated nanocarriers in the delivery of antifungal agents as an alternative to commercially available formulations. However, human clinical studies are needed to further confirm the safety profile, interactions and pharmacokinetic profile of the developed formulations with lipid-based nanocarriers.

Clinical and Regulatory Aspects Related to Dry Powder Inhalers against Pulmonary Aspergillosis

Clinical and Regulatory Aspects Related to Dry Powder Inhalers against Pulmonary Aspergillosis

The product has undergone Phase 1 clinical trials while the Phase 2 clinical trial was interrupted due to the COVID-19 pandemic [113,114].

Conclusions

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