mphram second semester

2. CONTENT
• INTRODUCTION
• HOW LUNGS WORK IN HUMAN BODY
• HOW DISEASE AFFECT TO LUNGS
• ADVANTAGES AND DISADVANTAGES
• SOME RESEARCH WORKS
• REFERENCES

3. INTRODUCTION
• Pulmonary drug delivery is a developing technology in which medication is inhaled
through the lungs and enters the bloodstream through the alveolar epithelium.
• The alveolar epithelium represents a physical barrier that protects from
environmental insults by segregating inhaled foreign agents and regulating water
and ions transport, thereby contributing to the maintenance of alveolar surface fluid
balance.
• Asthma and COPD(Chronic obstructive pulmonary disease) are the most common
disease occurred in lungs.(1)

4. • The treatment of asthma and COPD globally is dominated by the use of inhaled fixed-
dose combinations of a long-acting β2-agonist (LABA) and an inhaled corticosteroid
(ICS)
• Some of the most common inhaler types for asthma and COPD include corticosteroids,
beta-agonists, anticholinergic, and combination inhalers.(2)
• beclomethasone (Qvar)
• budesonide (Pulmicort Flex haler)
• ciclesonide (Alvesco)
• fluticasone (Flovent Diskus, Flovent HFA, Arnuity Ellipta)
• mometasone (Asmanex)

5. • Nanoparticle-mediated drug delivery systems open new perspectives by modifying the
physical properties of the particles, such as increasing the drug solubility, encapsulation
efficacy and surface alterations to enhance the drug release profiles and to obtain a
maximum effect.(3)

6. HOW LUNGS WORK IN HUMAN BODY
• Oxygen is moved into the bloodstream and carried through your body. At each cell
in your body, oxygen is exchanged for a waste gas called carbon dioxide. Your
bloodstream then carries this waste gas back to the lungs where it is removed from
the bloodstream and then exhaled.(4)

7. HOW DISEASES AFFECT TO LUNGS
• Asthma(wheezing and shortness of breath, allergies, infections),
• COPD, emphysema(this happens when the fragile links between alveoli are
damaged. Smoking is the usual cause.),
• Acute respiratory distress syndrome (ards) (this is a severe, sudden injury to the
lungs from a serious illness. COVID-19 is one example.) (5)

8. ADVANTAGES
• Rapid onset of action
• Avoidance of gastrointestinal upset
• Reduce systemic side effect due to
low concentration.
• Avoid first pass metabolism
DISADVANTAGES
• Complex delivery devices are used to
target drugs to the airways.
• Drug absorption may be limited by
the physical barrier of mucus layer.
• Mucociliary clearance reduce the
retention time of drugs.

9. ARTICLE:1Chitosan-coated nanoparticles enhanced lung pharmacokinetic profile of
voriconazole upon pulmonary delivery in mice
• Paramita Paul et al. 2019 were illustrated that Chitosan-coated polylactic-co-glycolic acid
nanoparticles of voriconazole (VChNP) were developed to increase residence time and
provide sustained drug release locally to treat recurrent lung-fungal infection.
• VChNP has been developed using a simple, unique technique and characterized.
Pharmacokinetics, lung deposition with time and gamma imaging were conducted with
optimized (6)

11. RESULT AND DISCUSSION
• The deposition of fluorescein iso thiocyanate-labeled VChNP in lung was confirmed
• by confocal microscopy. Gamma-scintigraphic images showed that Tc-99m-labeled
VChNP had better pulmonary retention for longer period than that of noncoated
formulation. Drastic improvement in pharmacokinetic profile of VChNP than
noncoated formulation was observed.
• Thus, VChNP may be useful for effective pulmonary delivery with improved
bioavailability. Such chitosan-coated nanoparticles may open up a new avenue for
efficacious treatment of lung-fungal infection

12. ARTICLE:2 Pulmonary Delivery of Voriconazole Loaded Nanoparticles Providing A
Prolonged Drug Level in Lungs- A Promise For Treating Fungal Infection
• Pranab Jyoti Das et al. 2015 stated that Current therapies are insufficient to prevent
recurrent fungal infection especially in the lower part of the lung. PLGA
nanoparticles containing antifungal drug voriconazole were prepared and two best
formulations were selected for further characterization and in vivo studies. The
nanoparticles and the free drug were radiolabeled with technetium-99m with
90% labeling efficiency.(7)

13. In vitro drug release profile (A) Cumulative percent drug released (% CDR) Vs. time
(days) in simulated lung fluid (pH 7.4); and (B) % CDR Vs. time (days) in phosphate
buffer (pH 7.4) from various nanoparticles formulations at different time points (data
as mean ± SD, n = 3).

14. RESULT AND DISCUSSION
• Voriconazole loaded nanoparticles are more efficacious to deliver the drug in
different lobes of lungs, as compared to the i.v. route of delivery. The nanoparticles
were subsequently radiolabeled with 99mTc. Administration of PLGA nanoparticles
leads to prolonged retention of particles in lungs with enhanced bio distribution.

15. ARTICLE : 3 Polymeric nanoparticles for the delivery of miRNA to treat Chronic
Obstructive Pulmonary Disease (COPD)
• Adel mohamed et al. 2019 stated that micro RNA (miRNA) may be tractable targets
for the treatment of chronic obstructive pulmonary disease (COPD) mir146a was
adsorbed onto poly (glycerol adipate-co-ω-pentadecalactone) to reduce target gene
IRAK1 expression. Nps were prepared using a single emulsion solvent evaporation
method incorporating cationic lipid di oleoyl trimethyl ammonium propane.(8)

16. miRNA in vitro release from 15% DOTAP NPs in
phosphate buffer saline at pH 7.4. Data presented as
Mean ± SD (n=3).
Cytotoxic effect of unloaded NPs (0% DOTAP) and 15% DOTAP NPs on A549 cells after 18
h incubation. DMSO was used as positive control; the cell viability was measured using MTT
assay. The experiments were repeated three times and data represented as mean ± SD (n=3), *p
< 0.05, ANOVA/ Turkey's to compare NPs with and without DOTAP at concentrations (0.312
mg, 0.625 mg, and 1.25 mg/ml).
RESULT AND DISCUSSION: miR-146a was successfully adsorbed onto PGA-co-PDL-
DOTAP NPs and retained biological activity after exposure to COPD. In vitro experiments
showed that loaded NPs could be used as a delivery system for miR-147a to treat COPD in
patients with the disease.

17. REFERENCES
1. Nanjwade BK, Adichwal SA, Gaikwad KR, Parikh KA, Manvi FV. Pulmonary drug delivery: novel pharmaceutical
technologies breathe new life into the lungs. PDA Journal of Pharmaceutical Science and Technology. 2011 Sep 1;65(5):513-
34.
2. https://www.medicalnewstoday.com/articles/inhaler-types
3. Paranjpe M, Müller-Goymann CC. Nanoparticle-mediated pulmonary drug delivery: a review. International journal of
molecular sciences. 2014 Apr 8;15(4):5852-73.
4. Faustino LD. Lungs—Inflammatory and respiratory system. InMacrophages in the Human Body 2022 Jan 1 (pp. 231-242).
Academic Press.
5. Graeff R, Guedes A, Quintana R, Wendt-Hornickle E, Baldo C, Walseth T, O’Grady S, Kannan M. Novel pathway of
adenosine generation in the lungs from NAD+: relevance to allergic airway disease. Molecules. 2020 Oct 27;25(21):4966.
6. Paul P, Sengupta S, Mukherjee B, Shaw TK, Gaonkar RH, Debnath MC. Chitosan-coated nanoparticles enhanced lung
pharmacokinetic profile of voriconazole upon pulmonary delivery in mice. Nanomedicine. 2018 Mar;13(5):501-20.
7. Das PJ, Paul P, Mukherjee B, Mazumder B, Mondal L, Baishya R, Debnath MC, Dey KS. Pulmonary delivery of
voriconazole loaded nanoparticles providing a prolonged drug level in lungs: a promise for treating fungal infection.
Molecular pharmaceutics. 2015 Aug 3;12(8):2651-64.
8. Mohamed A, Kunda NK, Ross K, Hutcheon GA, Saleem IY. Polymeric nanoparticles for the delivery of miRNA to treat
Chronic Obstructive Pulmonary Disease (COPD). European Journal of Pharmaceutics and Biopharmaceutics. 2019 Mar
1;136:1-8.