Revolutionizing the Treatment of Idiopathic Pulmonary Fibrosis: From Conventional Therapies to Advanced Drug Delivery Systems.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease that has been well-reported in the medical literature. Its incidence has risen, particularly in light of the recent COVID-19 pandemic. Conventionally, IPF is treated with antifibrotic drugs-pirfenidone and nintedanib-along with other drugs for symptomatic treatments, including corticosteroids, immunosuppressants, and bronchodilators based on individual requirements. Several drugs and biologicals such as fluorofenidone, thymoquinone, amikacin, paclitaxel nifuroxazide, STAT3, and siRNA have recently been evaluated for IPF treatment that reduces collagen formation and cell proliferation in the lung. There has been a great deal of research into various treatment options for pulmonary fibrosis using advanced delivery systems such as liposomal-based nanocarriers, chitosan nanoparticles, PLGA nanoparticles, solid lipid nanocarriers, and other nanoformulations such as metal nanoparticles, nanocrystals, cubosomes, magnetic nanospheres, and polymeric micelles. Several clinical trials are also ongoing for advanced IPF treatments. This article elaborates on the pathophysiology of IPF, its risk factors, and different advanced drug delivery systems for treating IPF. Although extensive preclinical data is available for these delivery systems, the clinical performance and scale-up studies would decide their commercial translation.

Long-circulating thiolated chitosan nanoparticles of nintedanib with N-acetyl cysteine for treating idiopathic pulmonary fibrosis: In vitro assessment of cytotoxicity, antioxidant, and antifibrotic potential.

Nintedanib (NIN) is one of the FDA-approved tyrosine kinase inhibitor drugs used to treat idiopathic pulmonary fibrosis (IPF). This study aimed to formulate a long-circulating injection of Nintedanib to treat bedridden patients with IPF. Nintedanib was incorporated into chitosan nanoparticles (NIN-NP) via the ionic gelation method, and N-acetyl cysteine (NAC), a known antioxidant and mucolytic agent, was added to the NIN-NP (NAC-NIN-NP). The lyophilized formulation had a particle size of 174 nm, a polydispersity index of 0.511, and a zeta potential of 18.6 mV. The spherical nanoparticles were observed in transmission electron microscopy, whereas field emission scanning electron microscopy showed irregular clusters of NP. The thiolation of the chitosan in NAC-NIN-NP was confirmed by ATR-FTIR and NMR, which improved drug release profiles showing >90 % drug release that was 2.42-folds greater than NIN-NP lasting for five days. The DPPH assay showed that adding NAC increased the % inhibition of oxidation in blank-NP (from 54.59 % to 87.17 %) and NIN-NP (58.65 %-89.19 %). The MTT assay on A549 cells showed 67.57 % cell viability by NAC-NIN-NP with an IC50 value of 28 µg/mL. The NAC formulation reduced hydroxyproline content (56.77 µg/mL) compared to NIN-NP (69.48 µg/mL) in WI-38 cell lines. Meanwhile, the healthy cells count with NAC-NIN-NP was higher (5.104 × 103) than with NIN-NP (4.878 × 103). In Hoechst staining, no significant damage to DNA was observed by the drug or formulation. Therefore, NAC-NIN-NP could be a promising treatment option for IPF patients and can be studied further clinically.

COVID-19-Associated Rhino-orbital mucormycosis: Presentation and outcome.

We are reporting four accounts of rhino-orbital mucormycosis in patients during and after recovery from SARS-CoV-2 infection. The patients were diagnosed and treated for COVID-19 according to the current treatment protocols, following which they presented with sudden proptosis, ophthalmoplegia, and conjunctival injection, confirmed by magnetic resonance imaging and histopathological examination. The patients were treated with intravenous liposomal amphotericin B, and the outcome was observed. Early diagnosis and prompt intervention can substantially reduce the morbidity and mortality rates in these patients.

Photo-activated chromophore for infectious keratitis cross-linking and its efficacy as a treatment modality in managing microbial keratitis.

Purpose: To assess Photo Activated Chromophore for Infective Keratitis-Cross Linking (PACK-CXL) and its efficacy as a treatment modality in managing microbial keratitis. Methods: Single Centre prospective interventional study in infectious keratitis. A total of eleven patients were taken who had corneal thickness (CT) more than 400µm. PACK-CXL was performed according to Dresden's protocol. The response was assessed by slit lamp examination, BCVA and AS-OCT at the time of complete healing. Results: The mean visual acuity at presentation was 1.207logMAR (0.3-3) which improved to mean value of 0.53logMAR (0.3-1). Mean time taken for complete epithelization was 17.45 days (14- 30 days) and that for complete healing was 33.72 days (21- 60 days). Mean CT at the baseline was 650.5± 108µm which reduced on consecutive follow up visits. There was reduction in the symptoms in nine patients except in two. One case reported increase in symptoms with worsening increase in endoexudates and hypopyon, and the other developed drug toxicity due to topical medications. Conclusion: Patients who underwent PACK-CXL showed good and early healing, good remodelling of cornea and improved visual acuity. The recalcitrant cases became responders to the same medications after PACK-CXL. Thus, PACK-CXL works well for both fungal and bacterial keratitis.