Abstract
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.
Similar content being viewed by others
References
Sung JC, Pulliam BL, Edwards DA (2007) Nanoparticles for drug delivery to the lungs. Trends Biotechnol 25:563–570
Azarmi S, Roa WH, Loebenberg R (2008) Targeted delivery of nanoparticles for the treatment of lung diseases. Adv Drug Deliv Rev 60:863–875
Rytting E, Nguyen J, Wang X, Kissel T (2008) Biodegradable polymeric nanocarriers for pulmonary drug delivery. Expert Opin Drug Deliv 5:629–639
Yang W, Peters JI, Williams III RO (2008) Inhaled nanoparticles—a current review. Int J Pharm 356:239–247
Lebhardt T, Roesler S, Beck-Broichsitter M, Kissel T (2010) Polymeric nanocarriers for drug delivery to the lung. J Drug Delivery Sci Technol 20:171–180
Roy I, Vij N (2010) Nanodelivery in airway diseases: challenges and therapeutic applications. Nanomedicine: NBM 6:237–244
Beck-Broichsitter M, Merkel OM, Kissel T (2012) Controlled pulmonary drug and gene delivery using polymeric nano-carriers. J Control Release 161:214–224
Clark A (2002) Formulation of proteins and peptides for inhalation. Drug Deliv Syst Sci 2:73–77
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. 269–300
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 70:329–339
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 269:457–467
Grenha A, Seijo B, Remuñán-López C (2005) Microencapsulated chitosan nanoparticles for lung protein delivery. Eur J Pharm Sci 25:427–437
Kwon GS (2003) Polymeric micelles for delivery of poorly water-soluble compounds. Crit Rev Ther Drug Carrier Syst 20:357–403
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 140:294–300
Batrakova EV, Kabanov AV (2008) Pluronic block copolymers: evolution of drug delivery concept from inert nanocarriers to biological response modifiers. J Control Release 130:98–106
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 33:3305–3313
Lin HR, Chang PC (2013) Novel Pluronic-chitosan micelle as an ocular delivery system. J Biomed Mater Res Part B 101B:689–699
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 239:183–192
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 158:329–335
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. 113–131
Courrier HM, Butz N, Vandamme TF (2002) Pulmonary drug delivery systems: recent developments and prospects. Crit Rev Ther Drug Carrier Syst 19:425–498
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 165:5760–5766
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 49:278–285
Ishwarya SP, Anandharamakrishnan C (2015) Spray-freeze-drying approach for soluble coffee processing and its effect on quality characteristics. J Food Eng 149:171–180
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
This study was not funded by any sources.
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Lin, HR., Li, YS. & Lin, YJ. Novel microencapsulated Pluronic–chitosan nanomicelles for lung delivery. Colloid Polym Sci 294, 1209–1216 (2016). https://doi.org/10.1007/s00396-016-3879-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00396-016-3879-6