Chronic
pulmonary diseases encompass different persistent and lethal
diseases, including chronic obstructive pulmonary disease (COPD),
idiopathic pulmonary fibrosis (IPF), cystic fibrosis (CF), asthma,
and lung cancers that affect millions of people globally. Traditional
pharmacotherapeutic treatment approaches (i.e., bronchodilators, corticosteroids,
chemotherapeutics, peptide-based agents, etc.) are not satisfactory
to cure or impede diseases. With the advent of nanotechnology, drug
delivery to an intended site is still difficult, but the nanoparticle’s
physicochemical properties can accomplish targeted therapeutic delivery.
Based on their surface, size, density, and physical-chemical properties,
nanoparticles have demonstrated enhanced pharmacokinetics of actives,
achieving the spotlight in the drug delivery research field. In this
review, the authors have highlighted different nanoparticle-based
therapeutic delivery approaches to treat chronic pulmonary diseases
along with the preparation techniques. The authors have remarked the
nanosuspension delivery via nebulization and dry powder carrier is
further effective in the lung delivery system since the particles
released from these systems are innumerable to composite nanoparticles.
The authors have also outlined the inhaled particle’s toxicity,
patented nanoparticle-based pulmonary formulations, and commercial
pulmonary drug delivery devices (PDD) in other sections. Recently
advanced formulations employing nanoparticles as therapeutic carriers
for the efficient treatment of chronic pulmonary diseases are also
canvassed.
The objectives of the present investigations are (1) to envisage a risk assessment plan for nonphospholipid-based topical ophthalmic emulsions with the help of failure mode and effect analysis (FMEA), (2) to screen the risky formulation and process variables by the Taguchi design, (3) to optimize systematically an emulsion formula by face-centered central composite design (CCD), (4) to incorporate cyclosporin A (0.05 or 0.1% w/w) into the optimized emulsions and predict the in vitro drug release kinetic via a particle diffusioncontrolled mathematical model equation, and (5) to assess the emulsion's toxicity using in vitro hemolysis study. Through the risk priority number (RPN) scores of FMEA, halfnormal and Pareto charts of the Taguchi design, 3D-response surface graphs, and overlay plots of CCD, the emulsion formula was systematically optimized. Irrespective of the two different drug loadings into optimized emulsions, the drug entrapment efficiency values ranged from 73.20 ± 0.13 to 74.42 ± 0.15%. The film diffusion or ion-exchange process fails to interpret the in vitro drug release kinetic profile. A permissible percentage hemolysis value of above 10% but below 25% guidance was observed for emulsions with or without cyclosporin A. The systematically optimized phospholipidless ophthalmic emulsions could further be exploited commercially for managing dry-eye syndrome.
Triple-negative breast cancer (TNBC) belongs to the category of the most destructive forms of breast cancer. Being a highly potent chemotherapeutic agent, paclitaxel (PTX) is extensively utilized in the management of various cancers. Commercially available PTX formulations contain non-targeted drug carriers that result in low antitumor activity because of non-specific tissue distribution. Thus, to resolve this issue, we designed PTX-loaded pH-sensitive liposomes (pH Lipos) in the present investigation and used adenosine (ADN) as a targeting ligand. Further, D-α-tocopheryl polyethylene glycol succinate (TPGS) was incorporated into the liposomes to impart a stealth effect to the system. For the development of these pH Lipos, different conjugates were synthesized (ADN-CHEMS and TPGS-ADN) and further utilized for the preparation of ADN-PEG-pH Lipo and ADN-pH Lipo by a thin-film hydration method. DOPE:HSPC:CHEMS:cholesterol at a molar ratio of 3:3:2:2 was selected for the preparation of pH-Lipo possessing 7.5% w/w drug loading. They showed a particle size below 140 nm, a PDI below 0.205, and a % EE greater than 60%. All of the pH Lipos displayed a biphasic pattern of PTX release at pH 7.4 and 5.5. However, the percent drug release at pH 5.5 was substantially greater because of the pH-sensitive nature of the liposomes. The MDA MB 231 and 4T1 cell lines depicted improvement in the qualitative as well as quantitative cellular uptake of PTX ADN-PEG-pH Lipo with a substantial decrease in the IC 50 value. Moreover, a higher apoptotic index was observed with pH Lipo compared to free PTX. PTX ADN-PEG-pH Lipo revealed a 3.98-and 3.41-fold rise in the AUC and t 1/2 values of PTX compared to Intaxel, respectively. Overall, characteristic decreases in tumor volume and serum toxicity marker levels were observed, which confirmed the development of an efficient and safe formulation.
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