Journal of Pharmaceutical Investigation

, Volume 45, Issue 2, pp 131–141 | Cite as

Layer-by-layer microcapsules for pH-controlled delivery of small molecules

  • Praveen Kumar Mandapalli
  • Venkata Vamsi Krishna Venuganti
Research Article
First Online:
Received:
Accepted:

Abstract

The aim of this study is to investigate the influence of pH on the encapsulation and release behavior of charged and neutral small molecules in layer-by-layer microcapsules (LbL-MC). Alternative layers of polystyrene sulfonate and polyallylamine hydrochloride polyelectrolytes were adsorbed onto calcium carbonate sacrificial templates. Six model small molecules including ascorbic acid, indomethacin, imatinib mesylate, rhodamine, 5-fluorouracil and estradiol were studied for their encapsulation in LbL-MC. Encapsulation efficiency was optimized for solute concentration, pH, incubation time and NaCl concentration. In vitro release studies were performed using dialysis membrane method at pH 4, 7.4 and 9. Optical microscopy and zetasizer results showed particles of 3.1 ± 0.2 μm diameter and 1.67 ± 0.87 mV potential. FTIR and differential scanning calorimeter studies confirmed the encapsulation of small molecules in LbL-MC. Encapsulation efficiency (%) of model molecules in LbL-MC increased with increase in solute concentration and increase in pH from 2 to 6. Interestingly, encapsulation efficiency was significantly greater for charged small molecules compared to neutral molecules. Extended release of charged molecules was achieved at pH 9. Kinetic modelling of release studies showed Fickian and non-Fickian diffusion of small molecules. In conclusion, LbL-MC can be developed as a potential carrier for small molecules depending on their physical and chemical properties.

Keywords

Layer-by-layer microcapsules Imatinib mesylate pH-responsive Encapsulation efficiency Polyelectrolytes 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

This article does not contain any studies with human and animal subjects performed by any of the authors. All authors (P.K. Mandapalli and V.V.K. Venuganti) declare that they have no conflict of interest. This work is financially supported by Department of Science and Technology, Science and Engineering Research Board-young scientist award (SERB/F/1260/2012–13). PK Mandapalli received CSIR-senior research fellowship for his doctoral studies.

References

  1. Bart G, Heleen D, Stefaan CDS, Ine L (2012) Crucial factors and emerging concepts in ultrasound-triggered drug delivery. J Control Release 164:248–255CrossRefGoogle Scholar
  2. Benjamin MW, Johan FJE (2012) Responsive layer-by-layer materials for drug delivery. J Control Release 158:2–14CrossRefGoogle Scholar
  3. Cai S, Thati S, Bagby TR, Diab HM, Davies NM, Cohen MS, Forrest ML (2010) Localized doxorubicin chemotherapy with a biopolymeric nanocarrier improves survival and reduces toxicity in xenografts of human breast cancer. J Control Release 146:212–218CrossRefPubMedCentralPubMedGoogle Scholar
  4. Cardone RA, Casavola V, Reshkin SJ (2005) The role of disturbed pH dynamics and the Na+/H+ exchanger in metastasis. Nat Rev Cancer 5:786–795CrossRefPubMedGoogle Scholar
  5. Chunhong Y, Olga S, Rossella C, Irina D, David LK, Vladimir VT (2011) Robust and responsive silk ionomer microcapsules. Biomacromolecules 12:4319–4325CrossRefGoogle Scholar
  6. Chunyin L, Bin M, Peng L (2011) Stimuli-responsive multilayer chitosan hollow microspheres via layer-by-layer assembly. Colloid Surf B 83:254–259CrossRefGoogle Scholar
  7. Clark SL, Hammond PT (2000) The role of secondary interactions in selective electrostatic multilayer deposition. Langmuir 16:10206–10214CrossRefGoogle Scholar
  8. Fukumura D, Jain RK (2007) Tumor microenvironment abnormalities: causes, consequences, and strategies to normalize. J Cell Biochem 101:937–949CrossRefPubMedGoogle Scholar
  9. Gan Q, Lu X, Dong W, Yuan Y, Qian J, Li Y, Shi J, Liu C (2012) Endosomal pH activatable magnetic nanoparticle-capped mesoporous silica for intracellular controlled release. J Mater Chem 22:15960–15968CrossRefGoogle Scholar
  10. Gao Z, Fain HD, Rapoport N (2004) Ultrasound-enhanced tumor targeting of polymeric micellar drug carriers. Mol Pharm 1:317–330CrossRefPubMedCentralPubMedGoogle Scholar
  11. Han B, Shen B, Wang Z, Shi M, Li H, Peng C, Zhao Q, Gao C (2008) Layered microcapsules for daunorubicin loading and release as well as in vitro and in vivo studies. Polym Adv Technol 19:36–46CrossRefGoogle Scholar
  12. Jia X, Yin J, He D, He X, Wang K, Chen M, Li Y (2013) Polyacrylic acid modified upconversion nanoparticles for simultaneous pH-triggered drug delivery and release imaging. J Biomed Nanotechnol 9:2063–2072CrossRefPubMedGoogle Scholar
  13. Kim JH, Li Y, Kim MS, Kang SW, Jeong JH, Lee DS (2012) Synthesis and evaluation of biotin-conjugated pH-responsive polymeric micelles as drug carriers. Int J Pharm 427:435–442CrossRefPubMedGoogle Scholar
  14. Kong SD, Sartor M, Hu CJ, Zhang W, Zhang L, Jin S (2013) Magnetic field activated lipid–polymer hybrid nanoparticles for stimuli-responsive drug release. Acta Biomater 9:5447–5452CrossRefPubMedCentralPubMedGoogle Scholar
  15. Kotov NA (1999) Layer-by-layer self-assembly: the contribution of hydrophobic interactions. Nano Struct Mater 12:789–796CrossRefGoogle Scholar
  16. Labala S, Mandapalli PK, Bhatnagar S, Venuganti VV (2014) Encapsulation of albumin in self-assembled layer-by-layer microcapsules: comparison of co-precipitation and adsorption techniques. Drug Dev Ind Pharm. doi: 10.3109/03639045.2014.947509 PubMedGoogle Scholar
  17. Liu J, Zhang Y, Wang C, Ruizhi X, Zhongping C, Ning G (2010) Magnetically sensitive alginate templated polyelectrolyte multilayer microcapsules for controlled release of doxorubicin. J Phys Chem C 114:7673–7679CrossRefGoogle Scholar
  18. Liu J, Pang Y, Huang W, Zhu Z, Zhu X, Zhou Y, Yan D (2011) Redox-responsive polyphosphate nanosized assemblies: a smart drug delivery platform for cancer therapy. Biomacromolecules 12:2407–2415CrossRefPubMedGoogle Scholar
  19. Mak WC, Cheung KY, Trau D (2008) Influence of different polyelectrolytes on layer-by-layer microcapsule properties: encapsulation efficiency and colloidal and temperature stability. Chem Mater 20:5475–5484CrossRefGoogle Scholar
  20. Manchun S, Dass CR, Sriamornsak P (2012) Targeted therapy for cancer using pH-responsive nanocarrier systems. Life Sci 90:381–387CrossRefPubMedGoogle Scholar
  21. Mandapalli PK, Labala S, Vanamala D, Koranglekar MP, Sakimalla LA, Venuganti VVK (2013) Influence of charge on encapsulation and release behavior of small molecules in self-assembled layer-by-layer microcapsules. Drug Deliv. doi: 10.3109/10717544.2013.867381 PubMedGoogle Scholar
  22. Manju S, Sreenivasan K (2011) Hollow microcapsules built by layer by layer assembly for the encapsulation and sustained release of curcumin. Colloid Surf B 82:588–593CrossRefGoogle Scholar
  23. Manna U, Patil S (2009) Dual drug delivery microcapsules via layer-by-layer self-assembly. Langmuir 25:10515–10522CrossRefPubMedGoogle Scholar
  24. Mao Z, Ma L, Gao C, Shen J (2005) Preformed microcapsules for loading and sustained release of ciprofloxacin hydrochloride. J Control Release 104:193–202CrossRefPubMedGoogle Scholar
  25. Matsumoto NM, Prabhakaran P, Rome LH, Maynard HD (2013) Smart vaults: thermally-responsive protein nanocapsules. ACS Nano 7:867–874CrossRefPubMedCentralPubMedGoogle Scholar
  26. Mihaela D, Helmuth M, Andre GS (2011) Stimuli-responsive LbL capsules and nanoshells for drug delivery. Adv Drug Deliv Rev 63:730–747CrossRefGoogle Scholar
  27. Peng L (2014) Stabilization of layer-by-layer engineered multi-layered hollow microspheres. Adv Colloid Interface Sci 207:178–188CrossRefGoogle Scholar
  28. Poon Z, Chang D, Zhao X, Hammond PT (2011) Layer-by-layer nanoparticles with a pH-sheddable layer for in vivo targeting of tumor hypoxia. ACS Nano 5:4284–4292CrossRefPubMedCentralPubMedGoogle Scholar
  29. Qinghe Z, Bingyun L (2008) pH-controlled drug loading and release from biodegradable microcapsules. Nanomedicine 4:302–310CrossRefGoogle Scholar
  30. Rao W, Zhang W, Poventud-Fuentes I, Wang Y, Lei Y, Agarwal P, Weekes B, Li C, Lu X, Yu J, He X (2014) Thermally responsive nanoparticle-encapsulated curcumin and its combination with mild hyperthermia for enhanced cancer cell destruction. Acta Biomater 10:831–842CrossRefPubMedCentralPubMedGoogle Scholar
  31. Rodrigues PCA, Beyer U, Schumacher P, Roth T, Fiebig HH, Unger C, Messori L, Orioli P, Paper DH, Mulhaupt R, Kratz F (1999) Acid-sensitive polyethylene glycol conjugates of doxorubicin: preparation, in vitro efficacy and intracellular distribution. Bioorg Med Chem 7:2517–2524CrossRefPubMedGoogle Scholar
  32. Santos JL, Nouri Fernandes T, Rodrigues J, Tomas H (2012) Gene delivery using biodegradable polyelectrolyte microcapsules prepared through the layer-by-layer technique. Biotechnol Prog 28:1088–1094CrossRefPubMedGoogle Scholar
  33. Sato M, Sano M (2005) van der Waals layer-by-layer construction of a carbon nanotube 2D network. Langmuir 21:11490–11494CrossRefPubMedGoogle Scholar
  34. Su X, Kim BS, Kim SR, Hammond PT, Irvine DJ (2009) Layer-by-layer assembled multilayer films for transcutaneous drug and vaccine delivery. ACS Nano 3:3719–3729CrossRefPubMedCentralPubMedGoogle Scholar
  35. Su J, Chen F, Cryns VL, Messersmith PB (2011) Catechol polymers for pH-responsive, targeted drug delivery to cancer cells. J Am Chem Soc 133:11850–11853CrossRefPubMedCentralPubMedGoogle Scholar
  36. Tao X, Chen H, Sun XJ, Chen JF, Roa WH (2007) Formulation and cytotoxicity of doxorubicin loaded in self-assembled bio-polyelectrolyte microshells. Int J Pharm 336:376–381CrossRefPubMedGoogle Scholar
  37. Veronika K, Eugenia K, Irina D, Derek C, Vladimir VT (2010) Responsive microcapsule reactors based on hydrogen-bonded tannic acid layer-by-layer assemblies. Soft Matter 6:3596–3608CrossRefGoogle Scholar
  38. Wang YC, Wang F, Sun TM, Wang J (2011) Redox-responsive nanoparticles from the single disulfide bond-bridged block copolymer as drug carriers for overcoming multidrug resistance in cancer cells. Bioconjug Chem 22:1939–1945CrossRefPubMedGoogle Scholar
  39. Weijun T, Changyou G, Helmuth M (2008) pH-responsive protein microcapsules fabricated via glutaraldehyde mediated covalent layer-by-layer assembly. Colloid Polym Sci 286:1103–1109CrossRefGoogle Scholar
  40. Yan S, Zhu J, Wang Z, Yin J, Zheng Y, Chen X (2011) Layer-by-layer assembly of poly (l-glutamic acid)/chitosan microcapsules for high loading and sustained release of 5-fluorouracil. Eur J Pharm Biopharm 78:336–345CrossRefPubMedGoogle Scholar
  41. Yang X, Grailer JJ, Pilla S, Steeber DA, Gong S (2010) Tumor-targeting, pH-responsive, and stable unimolecular micelles as drug nanocarriers for targeted cancer therapy. Bioconjug Chem 21:496–504CrossRefPubMedGoogle Scholar
  42. Yu F, Shilong B, Shuxun C, Dengli Q, Zhiqiang W, Xi Z (2002) Hydrogen-bonding directed layer by layer multilayer assembly: reconfirmation yielding microporous films. Macromolecules 35:9451–9458CrossRefGoogle Scholar
  43. Zhang XX, Eden HS, Chen X (2012) Peptides in cancer nanomedicine: drug carriers, targeting ligands and protease substrates. J Control Release 159:2–13CrossRefPubMedCentralPubMedGoogle Scholar
  44. Zhu L, Kate P, Torchilin VP (2012) Matrix metalloprotease-2 responsive multifunctional liposomal nanocarrier for enhanced tumor targeting. ACS Nano 6:3491–3498CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© The Korean Society of Pharmaceutical Sciences and Technology 2014

Authors and Affiliations

  • Praveen Kumar Mandapalli
    • 1
  • Venkata Vamsi Krishna Venuganti
    • 1
  1. 1.Department of PharmacyBITS PilaniHyderabadIndia

Personalised recommendations