Pluronic–chitosan micelles were subjected to spray-dryer to prepare microencapsulated nanomicelles for lung delivery using lactose as excipient. The physicochemical characterization of nanomicelles including diameter, surface charge, morphology, stability, aerodynamic diameter, and flow property were conducted. Pluronic–chitosan (Plu-Ch) micelles were prepared by changing the stirring rate and found that micelles prepared at 900 rpm have a diameter of about 408 nm, which is very suitable for further microencapsulation. Surfaces of micelle modified by chitosan carry positive charges which more readily adhere to the alveoli surface and hence increase bioavailability and enhance sustained release in the lungs. The most suitable ratios of lactose/micelles to prepare microencapsulated nanomicelles with the optimal aerodynamic diameter are 90:10 (4.22 μm) and 70:30 (4.53 μm). In vitro stability analysis indicates that once microencapsulated micelles enter the lung, they restore back to nanomicelles immediately and stay stable in the lung. The powders have good flowability and sustained drug release behavior with high release rates to maintain therapeutic concentration.
Pluronic Chitosan Micelle Lung delivery
This is a preview of subscription content, log in to check access.
Compliance with ethical standards
This study was not funded by any sources.
Conflict of interest
The authors declare that they have no conflict of interest.
Sung JC, Pulliam BL, Edwards DA (2007) Nanoparticles for drug delivery to the lungs. Trends Biotechnol 25:563–570CrossRefGoogle Scholar
Azarmi S, Roa WH, Loebenberg R (2008) Targeted delivery of nanoparticles for the treatment of lung diseases. Adv Drug Deliv Rev 60:863–875CrossRefGoogle Scholar
Rytting E, Nguyen J, Wang X, Kissel T (2008) Biodegradable polymeric nanocarriers for pulmonary drug delivery. Expert Opin Drug Deliv 5:629–639CrossRefGoogle Scholar
Yang W, Peters JI, Williams III RO (2008) Inhaled nanoparticles—a current review. Int J Pharm 356:239–247CrossRefGoogle Scholar
Lebhardt T, Roesler S, Beck-Broichsitter M, Kissel T (2010) Polymeric nanocarriers for drug delivery to the lung. J Drug Delivery Sci Technol 20:171–180CrossRefGoogle Scholar
Roy I, Vij N (2010) Nanodelivery in airway diseases: challenges and therapeutic applications. Nanomedicine: NBM 6:237–244Google Scholar
Beck-Broichsitter M, Merkel OM, Kissel T (2012) Controlled pulmonary drug and gene delivery using polymeric nano-carriers. J Control Release 161:214–224CrossRefGoogle Scholar
Clark A (2002) Formulation of proteins and peptides for inhalation. Drug Deliv Syst Sci 2:73–77Google Scholar
Taylor G, Kellaway I (2001) Pulmonary drug delivery. In: Hillery A, Lloyd A, Swarbrick J (eds) Drug delivery and targeting. Taylor & Francis, New York, pp. 269–300Google Scholar
Bosquillon C, Lombry C, Préat V, Vanbever R (2001) Influence of formulation excipients and physical characteristics of inhalation dry powders on their aerosolization performance. J Control Release 70:329–339CrossRefGoogle Scholar
Sham JO, Zhang Y, Finlay WH, Roa WH, Löbenberg R (2004) Formulation and characterization of spray-dried powders containing nanoparticles for aerosol delivery to the lung. Int J Pharm 269:457–467CrossRefGoogle Scholar
Grenha A, Seijo B, Remuñán-López C (2005) Microencapsulated chitosan nanoparticles for lung protein delivery. Eur J Pharm Sci 25:427–437CrossRefGoogle Scholar
Kwon GS (2003) Polymeric micelles for delivery of poorly water-soluble compounds. Crit Rev Ther Drug Carrier Syst 20:357–403CrossRefGoogle Scholar
Shin HC, Alani AW, Rao DA, Rockich NC, Kwon GS (2009) Multi-drug loaded polymeric micelles for simultaneous delivery of poorly soluble anticancer drugs. J Control Release 140:294–300CrossRefGoogle Scholar
Batrakova EV, Kabanov AV (2008) Pluronic block copolymers: evolution of drug delivery concept from inert nanocarriers to biological response modifiers. J Control Release 130:98–106CrossRefGoogle Scholar
Kozlov M, Melik-Nubarov N, Batrakova E, Kabanov A (2000) Relationship between Pluronic block copolymer structure, critical micellization concentration and partitioning coefficients of low molecular mass solutes. Macromolecules 33:3305–3313CrossRefGoogle Scholar
Lin HR, Chang PC (2013) Novel Pluronic-chitosan micelle as an ocular delivery system. J Biomed Mater Res Part B 101B:689–699CrossRefGoogle Scholar
Costa Silva LF, Kasten G, Maduro de Campos CE, Chinelatto AL, Lemos-Senna E (2013) Preparation and characterization of quercetin-loaded solid lipid microparticles for pulmonary delivery. Powder Technol 239:183–192CrossRefGoogle Scholar
Beck-Broichsitte M, Schweiger C, Schmehl T, Gessler T, Seeger W, Kisse T (2012) Characterization of novel spray-dried polymeric particles for controlled pulmonary drug delivery. J Control Release 158:329–335CrossRefGoogle Scholar
Ludwig MS (2008) Proteoglycans in the lung. In: Garg HG, Cowman MK, Hales CA (eds) Carbohydrate chemistry, biology and medical applications. Elsevier Ltd, New York, pp. 113–131CrossRefGoogle Scholar
Courrier HM, Butz N, Vandamme TF (2002) Pulmonary drug delivery systems: recent developments and prospects. Crit Rev Ther Drug Carrier Syst 19:425–498CrossRefGoogle Scholar
Akinbi HT, Epaud R, Bhatt H, Weaver TE (2000) Bacterial killing is enhanced by expression of lysozyme in the lungs of transgenic mice. J Immunol 165:5760–5766CrossRefGoogle Scholar
Scalia S, Haghi M, Losi V, Trotta V, Young PM, Traini D (2013) Quercetin solid lipid microparticles: a flavonoid for inhalation lung delivery. Eur J Pharm Sci 49:278–285CrossRefGoogle Scholar
Ishwarya SP, Anandharamakrishnan C (2015) Spray-freeze-drying approach for soluble coffee processing and its effect on quality characteristics. J Food Eng 149:171–180CrossRefGoogle Scholar