Skip to main content
Log in

Systemic and Mucosal Delivery of Drugs within Polymeric Microparticles Produced by Spray Drying

  • Review Article
  • Published:
BioDrugs Aims and scope Submit manuscript

Abstract

Encapsulation of therapeutic and diagnostic materials into polymeric particles is a means to protect and control or target the release of active substances such as drugs, vaccines, and genetic material. In terms of mucosal delivery, polymeric encapsulation can be used to promote absorption of the active substance, while particles can improve the half-life of drugs administered systemically. Spray drying is an attractive technology used to produce such microparticles, because it combines both the encapsulation and drying steps in a rapid, single-step operation. Even so, spray drying is not classically associated with processes used for drug and therapeutic material encapsulation, since elevated temperatures could potentially denature the active substance. However, a comprehensive review of the literature revealed a number of studies demonstrating that spray drying can be used to produce microparticulate formulations with labile therapeutics. Polymers commonly employed include synthetics such as methacrylic copolymers and polyesters, and natural materials including chitosan and alginate. Drugs and active substances are diverse and included antibiotics, anti-inflammatory agents, and chemotherapeutics. Regarding the delivery of spray-dried particles, the pulmonary, oral, colonic, and nasal mucosal routes are often investigated because they offer a convenient means of administration, which promotes physician and patient compliance. In addition, spray drying has been widely used to produce polymeric microparticles for systemic delivery in order to control the delivery of drugs, vaccines, or genetic material that may exhibit poor pharmacokinetic profiles or pose toxicity concerns. This review presents a brief introduction to the technology of spray drying and outlines the delivery routes and the applications of spray-dried polymeric microparticles.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Table I
Table II
Table III
Table IV
Table V
Table VI

Similar content being viewed by others

References

  1. Coppi G, Iannuccelli V, Leo E, et al. Protein immobilization in crosslinked alginate microparticles. J Microencapsul 2002 Jan–Feb; 19(1): 37–44

    Article  PubMed  CAS  Google Scholar 

  2. Sintov AC, Wormser U. Topical iodine facilitates transdermal delivery of insulin. J Control Release 2007 Apr; 118(2): 185–8

    Article  PubMed  CAS  Google Scholar 

  3. Pringels E, Callens C, Vervaet C, et al. Influence of deposition and spray pattern of nasal powders on insulin bioavailability. Int J Pharm 2006; 310(1-2): 1–7

    Article  PubMed  CAS  Google Scholar 

  4. Todo H, Okamoto H, Iida K, et al. Effect of additives on insulin absorption from intratracheally administered dry powders in rats. Int J Pharm 2001 Jun 4; 220(1-2): 101–10

    Article  PubMed  CAS  Google Scholar 

  5. Onuki Y, Morishita M, Takayama K, et al. In vivo effects of highly purified docosahexaenoic acid on rectal insulin absorption. Int J Pharm 2000 Apr 5; 198(2): 147–56

    Article  PubMed  CAS  Google Scholar 

  6. Damgé C, Maincent P, Ubrich N. Oral delivery of insulin associated to polymeric nanoparticles in diabetic rats. J Control Release 2007 Feb 12; 117(2): 163–70

    Article  PubMed  CAS  Google Scholar 

  7. Delie F, Blanco-Prieto MJ. Polymeric particles to improve oral bioavailability of peptide drugs. Molecules 2005; 10: 65–80

    Article  PubMed  CAS  Google Scholar 

  8. Morishita M, Peppas NA. Is the oral route possible for peptide and protein drug delivery? Drug Discov Today 2006 Oct; 11(19-20): 905–10

    Article  PubMed  CAS  Google Scholar 

  9. Hamman JH, Enslin GM, Kotze AF. Oral delivery of peptide drugs: barriers and developments. BioDrugs 2005; 19(3): 165–77

    Article  PubMed  CAS  Google Scholar 

  10. Pinto Reis C, Neufeld RJ, Ribeiro AJ, et al. Nanoencapsulation I. Methods for preparation of drug-loaded polymeric nanoparticles. Nanomedicine 2006 Mar; 2(1): 8–21

    Article  PubMed  CAS  Google Scholar 

  11. Cook RO, Pannu RK, Kellaway IW. Novel sustained release microspheres for pulmonary drug delivery. J Control Release 2005 May 5; 104(1): 79–90

    Article  PubMed  CAS  Google Scholar 

  12. Soppimath KS, Aminabhavi TM, Kulkarni AR, et al. Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release 2001 Jan 29; 70(1-2): 1–20

    Article  PubMed  CAS  Google Scholar 

  13. des Rieux A, Fievez V, Garinot M, et al. Nanoparticles as potential oral delivery systems of proteins and vaccines: a mechanistic approach. J Control Release 2006; 116(1): 1–27

    Article  PubMed  CAS  Google Scholar 

  14. Xie J, Wang CH. Encapsulation of proteins in biodegradable polymeric microparticles using electrospray in the Taylor cone-jet mode. Biotechnol Bioeng 2007 Aug 1; 97(5): 1278–90

    Article  PubMed  CAS  Google Scholar 

  15. Re MI. Microencapsulation by spray-drying. Drying Technol 1998; 16(16): 1195–36

    Article  CAS  Google Scholar 

  16. Peniche C, Argüelles-Monal W, Peniche H, et al. Chitosan: an attractive biocompatible polymer for microencapsulation. Macromol Biosci 2003 Oct; 3(10): 511–20

    Article  CAS  Google Scholar 

  17. Issa MM, Koping-Hoggard M, Tommeraas K, et al. Targeted gene delivery with trisaccharide-substituted chitosan oligomers in vitro and after lung administration in vivo. J Control Release 2006 Sep 28; 115(1): 103–12

    Article  PubMed  CAS  Google Scholar 

  18. Ventura CA, Tommasini S, Crupi E, et al. Chitosan microspheres for intrapulmonary administration of moxifloxacin: interaction with biomembrane models and in vitro permeation studies. Eur J Pharm Sci 2008 2; 68(2): 235–44

    CAS  Google Scholar 

  19. Tewa-Tagne P, Briancon S, Fessi H. Preparation of redispersible dry nano-capsules by means of spray-drying: development and characterisation. Eur J Pharm Sci 2007 Feb; 30(2): 124–35

    Article  PubMed  CAS  Google Scholar 

  20. Desai KG, Park HJ. Preparation of cross-linked chitosan microspheres by spray drying: effect of cross-linking agent on the properties of spray dried microspheres. J Microencapsul 2005 Jun; 22(4): 377–95

    Article  PubMed  CAS  Google Scholar 

  21. Zalfen AM, Nizet D, Jerome C, et al. Controlled release of drugs from multi-component biomaterials. Acta Biomater 2008 Nov; 4(6): 1788–96

    Article  PubMed  CAS  Google Scholar 

  22. Bies C, Lehr C, Woodley JF. Lectin-mediated drug targeting: history and applications. Adv Drug Deliv Rev 2004; 56(4): 425–35

    Article  PubMed  CAS  Google Scholar 

  23. O'Hagan DT, Singh M, Ulmer JB. Microparticle-based technologies for vaccines. Methods 2006 Sep; 40(1): 10–9

    Article  PubMed  CAS  Google Scholar 

  24. Singh M, Chakrapani A, O'Hagan D. Nanoparticles and microparticles as vaccine-delivery systems. Expert Rev Vaccines 2007 Oct; 6(5): 797–808

    Article  PubMed  CAS  Google Scholar 

  25. Lai SK, Wang YY, Hanes J. Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv Drug Deliv Rev 2009 Feb 27; 61(2): 158–71

    Article  PubMed  CAS  Google Scholar 

  26. Masters K. Spray-drying: an introduction to principles, operational practice and applications. 2nd ed. New York: John Wiley & Sons, 1976

    Google Scholar 

  27. Iskandar F, Gradon L, Okuyama K. Control of the morphology of nano-structured particles prepared by the spray drying of a nanoparticle sol. J Colloid Interface Sci 2003 Sep 15; 265(2): 296–303

    Article  PubMed  CAS  Google Scholar 

  28. Maa YF, Nguyen PA, Andya JD, et al. Effect of spray drying and subsequent processing conditions on residual moisture content and physical/biochemical stability of protein inhalation powders. Pharm Res 1998 May; 15(5): 768–75

    Article  PubMed  CAS  Google Scholar 

  29. Maa YF, Costantino HR, Nguyen PA, et al. The effect of operating and formulation variables on the morphology of spray-dried protein particles. Pharm Dev Technol 1997 Aug; 2(3): 213–23

    Article  PubMed  CAS  Google Scholar 

  30. Maa YF, Prestrelski SJ. Biopharmaceutical powders: particle formation and formulation considerations. Curr Pharm Biotechnol 2000 Nov; 1(3): 283–302

    Article  PubMed  CAS  Google Scholar 

  31. Baras B, Benoit MA, Gillard J. Parameters influencing the antigen release from spray-dried poly(DL-lactide) microparticles. Int J Pharm 2000 Apr 25; 200(1): 133–45

    Article  PubMed  CAS  Google Scholar 

  32. Okuyama K, Lenggoro IW. Preparation of nanoparticles via spray route. Chem Eng Sci 2003; 58: 537–47

    Article  CAS  Google Scholar 

  33. Ré M. Formulating drug delivery systems by spray drying. Drying Technol 2006; 24(4): 433–46

    Article  CAS  Google Scholar 

  34. Reis CP, Neufeld RJ, Vilela S, et al. Review and current status of emulsion/dispersion technology using an internal gelation process for the design of alginate particles. J Microencapsul 2006 May; 23(3): 245–57

    Article  PubMed  CAS  Google Scholar 

  35. Johansen P, Merkle HP, Gander B. Technological considerations related to the up-scaling of protein microencapsulation by spray-drying. Eur J Pharm Biopharm 2000 Nov; 50(3): 413–7

    Article  PubMed  CAS  Google Scholar 

  36. Lam XM, Duenas ET, Cleland JL. Encapsulation and stabilization of nerve growth factor into poly(lactic-co-glycolic) acid microspheres. J Pharm Sci 2001 Sep; 90(9): 1356–65

    Article  PubMed  CAS  Google Scholar 

  37. Balmayor ER, Tuzlakoglu K, Azevedo HS, et al. Preparation and characterization of starch-poly-epsilon-caprolactone microparticles incorporating bioactive agents for drug delivery and tissue engineering applications. Acta Biomater 2009 May; 5(4): 1035–45

    Article  PubMed  CAS  Google Scholar 

  38. Sadeghi AM, Dorkoosh FA, Avadi MR, et al. Preparation, characterization and antibacterial activities of chitosan, N-trimethyl chitosan (TMC) and N-diethylmethyl chitosan (DEMC) nanoparticles loaded with insulin using both the ionotropic gelation and polyelectrolyte complexation methods. Int J Pharm 2008 May 1; 355(1-2): 299–306

    Article  PubMed  CAS  Google Scholar 

  39. Kondo M, Niwa T, Okamoto H, et al. Particle characterization of poorly water-soluble drugs using a spray freeze drying technique. Chem Pharm Bull (Tokyo) 2009 Jul; 57(7): 657–62

    Article  CAS  Google Scholar 

  40. Maltesen MJ, Bjerregaard S, Hovgaard L, et al. Quality by design: spray drying of insulin intended for inhalation. Eur J Pharm Biopharm 2008 Nov; 70(3): 828–38

    Article  PubMed  CAS  Google Scholar 

  41. Kusonwiriyawong C, Pichayakorn W, Lipipun V, et al. Retained integrity of protein encapsulated in spray-dried chitosan microparticles. J Microencapsul 2009 Mar; 26(2): 111–21

    Article  PubMed  CAS  Google Scholar 

  42. Tewa-Tagne P, Briançon S, Fessi H. Spray-dried microparticles containing polymeric nanocapsules: formulation aspects, liquid phase interactions and particles characteristics. Int J Pharm 2006; 325(1-2): 63–74

    Article  PubMed  CAS  Google Scholar 

  43. Giunchedi P, Alpar HO, Conte U. PDLLA microspheres containing steroids: spray-drying, o/w and w/o/w emulsifications as preparation methods. J Microencapsul 1998 Mar–Apr; 15(2): 185–95

    Article  PubMed  CAS  Google Scholar 

  44. Motlekar N, Youan BB. Optimization of experimental parameters for the production of LMWH-loaded polymeric microspheres. Drug Des Devel Ther 2009 Feb 6; 2: 39–47

    PubMed  Google Scholar 

  45. Le Corre P, Estebe JP, Clement R, et al. Spray-dryed bupivacaine-loaded microspheres: in vitro evaluation and biopharmaceutics of bupivacaine following brachial plexus administration in sheep. Int J Pharm 2002 May 15; 238(1-2): 191–203

    Article  PubMed  Google Scholar 

  46. Conti B, Bucolo C, Giannavola C, et al. Biodegradable microspheres for the intravitreal administration of acyclovir: in vitro/in vivo evaluation. Eur J Pharm Sci 1997; 5: 287–93

    Article  CAS  Google Scholar 

  47. Bain DF, Munday DL, Smith A. Modulation of rifampicin release from spray-dried microspheres using combinations of poly-(DL-lactide). J Microencapsul 1999 May–Jun; 16(3): 369–85

    Article  PubMed  CAS  Google Scholar 

  48. Baras B, Benoit M, Poulain-Godefroy O, et al. Vaccine properties of antigens entrapped in microparticles produced by spray-drying technique and using various polyester polymers. Vaccine 2000 Feb 14; 18(15): 1495–505

    Article  PubMed  CAS  Google Scholar 

  49. Wagenaar BW, Muller BW. Piroxicam release from spray-dried biodegradable microspheres. Biomaterials 1994 Jan; 15(1): 49–54

    Article  PubMed  CAS  Google Scholar 

  50. Wang FJ, Wang CH. Effects of fabrication conditions on the characteristics of etanidazole spray-dried microspheres. J Microencapsul 2002 Jul–Aug; 19(4): 495–510

    Article  PubMed  CAS  Google Scholar 

  51. Zgoulli S, Grek V, Barre G, et al. Microencapsulation of erythromycin and clarithromycin using a spray-drying technique. J Microencapsul 1999 Sep-Oct; 16(5): 565–71

    Article  PubMed  CAS  Google Scholar 

  52. Giunchedi P, Genta I, Conti B, et al. Preparation and characterization of ampicillin loaded methylpyrrolidinone chitosan and chitosan microspheres. Biomaterials 1998 Jan–Feb; 19(1-3): 157–61

    Article  PubMed  CAS  Google Scholar 

  53. Ameri M, Yuh-Fun Maa. Spray drying of biopharmaceuticals: stability and process considerations. Drying Technol 2006; 24(6): 763–8

    Article  CAS  Google Scholar 

  54. Patel N, Craddock BL, Staniforth JN, et al. Spray-dried insulin particles retain biological activity in rapid in-vitro assay. J Pharm Pharmacol 2001 Oct; 53(10): 1415–8

    Article  PubMed  CAS  Google Scholar 

  55. Shoyele SA, Cawthorne S. Particle engineering techniques for inhaled biopharmaceuticals. Adv Drug Deliv Rev 2006 Oct 31; 58(9-10): 1009–29

    Article  PubMed  CAS  Google Scholar 

  56. Huang YC, Chiang CH, Yeh MK. Optimizing formulation factors in preparing chitosan microparticles by spray-drying method. J Microencapsul 2003 Mar–Apr; 20(2): 247–60

    PubMed  CAS  Google Scholar 

  57. Stahl K, Claesson M, Lilliehorn P, et al. The effect of process variables on the degradation and physical properties of spray dried insulin intended for inhalation. Int J Pharm 2002 Feb 21; 233(1-2): 227–37

    Article  PubMed  CAS  Google Scholar 

  58. Vehring R. Pharmaceutical particle engineering via spray drying. Pharm Res 2008 May; 25(5): 999–1022

    Article  PubMed  CAS  Google Scholar 

  59. Wan LSC, Heng PWS, Chia CGH. Preparation of coated particles using a spray drying process with an aqueous system. Int J Pharm 1991; 77(2-3): 183–91

    Article  CAS  Google Scholar 

  60. Billon A, Bataille B, Cassanas G, et al. Development of spray-dried acetaminophen microparticles using experimental designs. Int J Pharm 2000 Aug 10; 203(1-2): 159–68

    Article  PubMed  CAS  Google Scholar 

  61. Nettey H, Haswani D, Oettinger CW, et al. Formulation and testing of vancomycin loaded albumin microspheres prepared by spray-drying. J Microencapsul 2006 Sep; 23(6): 632–42

    Article  PubMed  CAS  Google Scholar 

  62. Piao MG, Yang CW, Li DX, et al. Preparation and in vivo evaluation of piroxicam-loaded gelatin microcapsule by spray drying technique. Biol Pharm Bull 2008 Jun; 31(6): 1284–7

    Article  PubMed  CAS  Google Scholar 

  63. Martinac A, Filipovic-Grcic J, Perissutti B, et al. Spray-dried chitosan/ethylcellulose microspheres for nasal drug delivery: swelling study and evaluation of in vitro drug release properties. J Microencapsul 2005 Aug; 22(5): 549–61

    Article  PubMed  CAS  Google Scholar 

  64. Pignatello R, Amico D, Chiechio S, et al. Preparation and analgesic activity of Eudragit RS100 microparticles containing diflunisal. Drug Deliv 2001 Jan–Mar; 8(1): 35–45

    Article  PubMed  CAS  Google Scholar 

  65. Palmieri GF, Bonacucina G, Di Martino P, et al. Gastro-resistant microspheres containing ketoprofen. J Microencapsul 2002 Jan–Feb; 19(1): 111–9

    Article  PubMed  CAS  Google Scholar 

  66. Esposito E, Cervellati F, Menegatti E, et al. Spray dried Eudragit microparticles as encapsulation devices for vitamin C. Int J Pharm 2002 Aug 21; 242(1-2): 329–34

    Article  PubMed  CAS  Google Scholar 

  67. Esposito E, Roncarati R, Cortesi R, et al. Production of Eudragit microparticles by spray-drying technique: influence of experimental parameters on morphological and dimensional characteristics. Pharm Dev Technol 2000; 5(2): 267–78

    Article  PubMed  CAS  Google Scholar 

  68. Walter E, Moelling K, Pavlovic J, et al. Microencapsulation of DNA using poly(DL-lactide-co-glycolide): stability issues and release characteristics. J Control Release 1999 Sep 20; 61(3): 361–74

    Article  PubMed  CAS  Google Scholar 

  69. Murillo M, Gamazo C, Goni M, et al. Development of microparticles prepared by spray-drying as a vaccine delivery system against brucellosis. Int J Pharm 2002 Aug 21; 242(1-2): 341–4

    Article  PubMed  CAS  Google Scholar 

  70. Li Z, Li Q, Simon S, et al. Formulation of spray-dried phenytoin loaded poly(epsilon-caprolactone) microcarrier intended for brain delivery to treat epilepsy. J Pharm Sci 2007 May; 96(5): 1018–30

    Article  PubMed  CAS  Google Scholar 

  71. Mok H, Park TG. Water-free microencapsulation of proteins within PLGA microparticles by spray drying using PEG-assisted protein solubilization technique in organic solvent. Eur J Pharm Biopharm 2008 Sep; 70(1): 137–44

    Article  PubMed  CAS  Google Scholar 

  72. Gibaud S, Jabir Al Awwadi N, Ducki C, et al. Poly(ε-caprolactone) and Eudragit® microparticles containing fludrocortisone acetate. Int J Pharm 2004; 269(2): 491–508

    Article  PubMed  CAS  Google Scholar 

  73. Coccoli V, Luciani A, Orsi S, et al. Engineering of poly(epsilon-caprolactone) microcarriers to modulate protein encapsulation capability and release kinetic. J Mater Sci Mater Med 2008 Apr; 19(4): 1703–11

    Article  PubMed  CAS  Google Scholar 

  74. Sinha VR, Trehan A. Formulation, characterization, and evaluation of ketorolac tromethamine-loaded biodegradable microspheres. Drug Deliv 2005 May–Jun; 12(3): 133–9

    Article  PubMed  CAS  Google Scholar 

  75. Giunchedi P, Conti B, Maggi L, et al. Cellulose acetate butyrate and polycaprolactone for ketoprofen spray-dried microsphere preparation. J Microencapsul 1994 Jul–Aug; 11(4): 381–93

    Article  PubMed  CAS  Google Scholar 

  76. Luzardo-Alvarez A, Almeida-Prieto S, Fraga-López F, et al. Effect of formulation variables on the prediction of release from microparticles with experimental design. J Appl Polym Sci 2006 Dec 5; 102(5): 4546–53

    Article  CAS  Google Scholar 

  77. Raj NKK, Sharma CP. Oral insulin: a perspective. J Biomater Appl 2003 Jan 1; 17(3): 183–96

    Article  PubMed  CAS  Google Scholar 

  78. Park JH, Ye M, Park K. Biodegradable polymers for microencapsulation of drugs. Molecules 2005 Jan 31; 10(1): 146–61

    Article  PubMed  CAS  Google Scholar 

  79. Sivadas N, O'Rourke D, Tobin A, et al. A comparative study of a range of polymeric microspheres as potential carriers for the inhalation of proteins. Int J Pharm 2008; 358(1-2): 159–67

    Article  PubMed  CAS  Google Scholar 

  80. Baras B, Benoit MA, Gillard J. Influence of various technological parameters on the preparation of spray-dried poly(epsilon-caprolactone) microparticles containing a model antigen. J Microencapsul 2000 Jul–Aug; 17(4): 485–98

    Article  PubMed  CAS  Google Scholar 

  81. O'Hagan DT. Microparticles and polymers for the mucosal delivery of vaccines. Adv Drug Deliv Rev 1998; 34(2-3): 305–20

    Article  PubMed  Google Scholar 

  82. Vajdy M, O'Hagan DT. Microparticles for intranasal immunization. Adv Drug Deliv Rev 2001 Sep 23; 51(1-3): 127–41

    Article  PubMed  CAS  Google Scholar 

  83. Olson WP, editor. Separations technology: pharmaceutical and biotechnology applications. 1st ed. Buffalo Grove (IL): CRC Press, 1995

    Google Scholar 

  84. Hejazi R, Amiji M. Chitosan-based gastrointestinal delivery systems. J Control Release 2003 Apr 29; 89(2): 151–65

    Article  PubMed  CAS  Google Scholar 

  85. Zhang WF, Chen XG, Li PW, et al. Preparation and characterization of theophylline loaded chitosan/beta-cyclodextrin microspheres. J Mater Sci Mater Med 2008 Jan; 19(1): 305–10

    Article  PubMed  CAS  Google Scholar 

  86. Ma Z, Lim TM, Lim LY. Pharmacological activity of peroral chitosan-insulin nanoparticles in diabetic rats. Int J Pharm 2005 Apr 11; 293(1-2): 271–80

    Article  PubMed  CAS  Google Scholar 

  87. Lin YH, Mi FL, Chen CT, et al. Preparation and characterization of nanoparticles shelled with chitosan for oral insulin delivery. Biomacromolecules 2007 Jan; 8(1): 146–52

    Article  PubMed  CAS  Google Scholar 

  88. Pan Y, Li YJ, Zhao HY, et al. Bioadhesive polysaccharide in protein delivery system: chitosan nanoparticles improve the intestinal absorption of insulin in vivo. Int J Pharm 2002 Dec 5; 249(1-2): 139–47

    Article  PubMed  CAS  Google Scholar 

  89. Huang YC, Yeh MK, Cheng SN, et al. The characteristics of betamethasone-loaded chitosan microparticles by spray-drying method. J Microencapsul 2003 Jul–Aug; 20(4): 459–72

    Article  PubMed  CAS  Google Scholar 

  90. Learoyd TP, Burrows JL, French E, et al. Chitosan-based spray-dried respirable powders for sustained delivery of terbutaline sulfate. Eur J Pharm Biopharm 2008 Feb; 68(2): 224–34

    Article  PubMed  CAS  Google Scholar 

  91. Wee S, Gombotz WR. Protein release from alginate matrices. Adv Drug Deliv Rev 1998 May 4; 31(3): 267–85

    Article  PubMed  Google Scholar 

  92. Sarmento B, Ferreira D, Veiga F, et al. Characterization of insulin-loaded alginate nanoparticles produced by ionotropic pre-gelation through DSC and FTIR studies. Carbohydr Polym 2006; 66(1): 1–7

    Article  CAS  Google Scholar 

  93. George M, Abraham TE. Polyionic hydrocolloids for the intestinal delivery of protein drugs: alginate and chitosan — a review. J Control Release 2006; 114(1): 1–14

    Article  PubMed  CAS  Google Scholar 

  94. Augst AD, Kong HJ, Mooney DJ. Alginate hydrogels as biomaterials. Macromol Biosci 2006 Aug 7; 6(8): 623–33

    Article  PubMed  CAS  Google Scholar 

  95. Gacesa P. Alginates. Carbohydr Polym 1988; 8(3): 161–82

    Article  CAS  Google Scholar 

  96. Azarmi S, Roa WH, Lobenberg R. Targeted delivery of nanoparticles for the treatment of lung diseases. Adv Drug Deliv Rev 2008 May 22; 60(8): 863–75

    Article  PubMed  CAS  Google Scholar 

  97. Buttini F, Colombo P, Wenger MP, et al. Back to basics: the development of a simple, homogenous, two-component dry-powder inhaler formulation for the delivery of budesonide using miscible vinyl polymers. J Pharm Sci 2008 Mar; 97(3): 1257–67

    Article  PubMed  CAS  Google Scholar 

  98. Tomoda K, Ohkoshi T, Nakajima T, et al. Preparation and properties of inhalable nanocomposite particles: effects of the size, weight ratio of the primary nanoparticles in nanocomposite particles and temperature at a spray-dryer inlet upon properties of nanocomposite particles. Colloids Surf B Biointerfaces 2008 Jun 15; 64(1): 70–6

    Article  PubMed  CAS  Google Scholar 

  99. Seville PC, Kellaway IW, Birchall JC. Preparation of dry powder dispersions for non-viral gene delivery by freeze-drying and spray-drying. J Gene Med 2002 Jul–Aug; 4(4): 428–37

    Article  PubMed  CAS  Google Scholar 

  100. Li X, Guo Q, Zheng X, et al. Preparation of honokiol-loaded chitosan microparticles via spray-drying method intended for pulmonary delivery. Drug Deliv 2009 Apr; 16(3): 160–6

    Article  PubMed  CAS  Google Scholar 

  101. Learoyd TP, Burrows JL, French E, et al. Modified release of beclometasone dipropionate from chitosan-based spray-dried respirable powders. Powder Technol 2008; 187(3): 231–8

    Article  CAS  Google Scholar 

  102. Rivera PA, Martinez-Oharriz MC, Rubio M, et al. Fluconazole encapsulation in PLGA microspheres by spray-drying. J Microencapsul 2004 Mar; 21(2): 203–11

    Article  PubMed  CAS  Google Scholar 

  103. Sung JC, Pulliam BL, Edwards DA. Nanoparticles for drug delivery to the lungs. Trends Biotechnol 2007 Dec; 25(12): 563–70

    Article  PubMed  CAS  Google Scholar 

  104. Grenha A, Seijo B, Remunan-Lopez C. Microencapsulated chitosan nanoparticles for lung protein delivery. Eur J Pharm Sci 2005 Jul–Aug; 25(4-5): 427–37

    Article  PubMed  CAS  Google Scholar 

  105. Adi H, Young PM, Chan HK, et al. Cospray dried antibiotics for dry powder lung delivery. J Pharm Sci 2008 Aug; 97(8): 3356–66

    Article  PubMed  CAS  Google Scholar 

  106. Grenha A, Remunan-Lopez C, Carvalho EL, et al. Microspheres containing lipid/chitosan nanoparticles complexes for pulmonary delivery of therapeutic proteins. Eur J Pharm Biopharm 2008 May; 69(1): 83–93

    Article  PubMed  CAS  Google Scholar 

  107. Chalasani KB, Russell-Jones GJ, Yandrapu SK, et al. A novel vitamin B12-nanosphere conjugate carrier system for peroral delivery of insulin. J Control Release 2007 Feb 26; 117(3): 421–9

    Article  PubMed  CAS  Google Scholar 

  108. Sadrzadeh N, Glembourtt MJ, Stevenson CL. Peptide drug delivery strategies for the treatment of diabetes. J Pharm Sci 2007 Aug; 96(8): 1925–54

    Article  PubMed  CAS  Google Scholar 

  109. Chen H, Langer R. Oral particulate delivery: status and future trends. Adv Drug Deliv Rev 1998 Dec 1; 34(2-3): 339–50

    Article  PubMed  CAS  Google Scholar 

  110. Anal AK, Stevens WF, Remuñán-López C. Ionotropic cross-linked chitosan microspheres for controlled release of ampicillin. Int J Pharm 2006; 312(1-2): 166–73

    Article  PubMed  CAS  Google Scholar 

  111. Elvassore N, Bertucco A, Caliceti P. Production of insulin-loaded poly(-ethylene glycol)/poly(l-lactide) (PEG/PLA) nanoparticles by gas antisolvent techniques. J Pharm Sci 2001 Oct; 90(10): 1628–36

    Article  PubMed  CAS  Google Scholar 

  112. Dea-Ayuela MA, Rama-Iniguez S, Torrado-Santiago S, et al. Microcapsules formulated in the enteric coating copolymer Eudragit L100 as delivery systems for oral vaccination against infections by gastrointestinal nematode parasites. J Drug Target 2006 Sep; 14(8): 567–75

    Article  PubMed  CAS  Google Scholar 

  113. Palmieri GF, Bonacucina G, Di Martino P, et al. Spray-drying as a method for microparticulate controlled release systems preparation: advantages and limits. I. Water-soluble drugs. Drug Dev Ind Pharm 2001; 27(3): 195–204

    Article  PubMed  CAS  Google Scholar 

  114. Rattes ALR, Oliveira WP. Spray drying conditions and encapsulating composition effects on formation and properties of sodium diclofenac microparticles. Powder Technology 2007; 171(1): 7–14

    Article  CAS  Google Scholar 

  115. Mardziah RE, Wong TW. Effects of microwave on drug-release responses of spray-dried alginate microspheres. Drug Dev Ind Pharm. Epub 2010 Apr 12

  116. Simonoska Crcarevska M, Glavas Dodov M, Petrusevska G, et al. Bioefficacy of budesonide loaded crosslinked polyelectrolyte microparticles in rat model of induced colitis. J Drug Target 2009 Dec; 17(10): 788–802

    Article  PubMed  CAS  Google Scholar 

  117. Simonoska Crcarevska M, Glavas Dodov M, Goracinova K. Chitosan coated Ca-alginate microparticles loaded with budesonide for delivery to the inflamed colonic mucosa. Eur J Pharm Biopharm 2008; 68(3): 565–78

    Article  PubMed  CAS  Google Scholar 

  118. Coppi G, Bondi M, Coppi A, et al. Toxicity and gut associated lymphoid tissue translocation of polymyxin B orally administered by alginate/chitosan microparticles in rats. J Pharm Pharmacol 2008 Jan; 60(1): 21–6

    Article  PubMed  CAS  Google Scholar 

  119. Desai KG, Park HJ. Effect of manufacturing parameters on the characteristics of vitamin C encapsulated tripolyphosphate-chitosan microspheres prepared by spray-drying. J Microencapsul 2006 Feb; 23(1): 91–103

    Article  PubMed  CAS  Google Scholar 

  120. Raffin RP, Jornada DS, Re MI, et al. Sodium pantoprazole-loaded enteric microparticles prepared by spray drying: effect of the scale of production and process validation. Int J Pharm 2006 Oct 31; 324(1): 10–8

    Article  PubMed  CAS  Google Scholar 

  121. Coppi G, Iannuccelli V, Sala N, et al. Alginate microparticles for Polymyxin B Peyer's patches uptake: microparticles for antibiotic oral administration. J Microencapsul 2004 Dec; 21(8): 829–39

    Article  PubMed  CAS  Google Scholar 

  122. Gavini E, Sanna V, Juliano C, et al. Compressed biodegradable matrices of spray-dried PLGA microspheres for the modified release of ketoprofen. J Microencapsul 2003 Mar–Apr; 20(2): 193–201

    PubMed  CAS  Google Scholar 

  123. Moretti MD, Gavini E, Juliano C, et al. Spray-dried microspheres containing ketoprofen formulated into capsules and tablets. J Microencapsul 2001 Jan–Feb; 18(1): 111–21

    Article  PubMed  CAS  Google Scholar 

  124. Bigucci F, Luppi B, Monaco L, et al. Pectin-based microspheres for colon-specific delivery of vancomycin. J Pharm Pharmacol 2009 Jan; 61(1): 41–6

    Article  PubMed  CAS  Google Scholar 

  125. Lorenzo-Lamosa ML, Remuñán-López C, Vila-Jato JL, et al. Design of microencapsulated chitosan microspheres for colonic drug delivery. J Control Release 1998; 52(1-2): 109–18

    Article  PubMed  CAS  Google Scholar 

  126. Takeuchi H, Yasuji T, Yamamoto H, et al. Spray-dried lactose composite particles containing an ion complex of alginate-chitosan for designing a dry-coated tablet having a time-controlled releasing function. Pharm Res 2000 Jan; 17(1): 94–9

    Article  PubMed  CAS  Google Scholar 

  127. Mladenovska K, Cruaud O, Richomme P, et al. 5-ASA loaded chitosan-Ca-alginate microparticles: preparation and physicochemical characterization. Int J Pharm 2007 Dec 10; 345(1-2): 59–69

    Article  PubMed  CAS  Google Scholar 

  128. Lu B, Zhang Z. Novel colon-specific microspheres with highly dispersed hydroxycamptothecin cores: their preparation, release behavior, and therapeutic efficiency against colonic cancer. J Pharm Sci 2006 Dec; 95(12): 2619–30

    Article  PubMed  CAS  Google Scholar 

  129. Gavini E, Chetoni P, Cossu M, et al. PLGA microspheres for the ocular delivery of a peptide drug, vancomycin using emulsification/spray-drying as the preparation method: in vitro/in vivo studies. Eur J Pharm Biopharm 2004 Mar; 57(2): 207–12

    Article  PubMed  CAS  Google Scholar 

  130. Dalpiaz A, Gavini E, Colombo G, et al. Brain uptake of an anti-ischemic agent by nasal administration of microparticles. J Pharm Sci 2008 Nov; 97(11): 4889–903

    Article  PubMed  CAS  Google Scholar 

  131. Gavini E, Rassu G, Muzzarelli C, et al. Spray-dried microspheres based on methylpyrrolidinone chitosan as new carrier for nasal administration of metoclopramide. Eur J Pharm Biopharm 2008 Feb; 68(2): 245–52

    Article  PubMed  CAS  Google Scholar 

  132. Illum L, Jørgensen H, Bisgaard H, et al. Bioadhesive microspheres as a potential nasal drug delivery system. Int J Pharm 1987; 39(3): 189–99

    Article  CAS  Google Scholar 

  133. Cerchiara T, Luppi B, Chidichimo G, et al. Chitosan and poly(methyl vinyl ether-co-maleic anhydride) microparticles as nasal sustained delivery systems. Eur J Pharm Biopharm 2005; 61(3): 195–200

    Article  PubMed  CAS  Google Scholar 

  134. Alhalaweh A, Andersson S, Velaga SP. Preparation of zolmitriptan-chitosan microparticles by spray drying for nasal delivery. Eur J Pharm Sci 2009 Oct 8; 38(3): 206–14

    Article  PubMed  CAS  Google Scholar 

  135. Coucke D, Vervaet C, Foreman P, et al. Effect on the nasal bioavailability of co-processing drug and bioadhesive carrier via spray-drying. Int J Pharm 2009 Sep 8; 379(1): 67–71

    Article  PubMed  CAS  Google Scholar 

  136. Jain SA, Chauk DS, Mahajan HS, et al. Formulation and evaluation of nasal mucoadhesive microspheres of sumatriptan succinate. J Microencapsul 2009 Dec; 26(8): 711–21

    Article  PubMed  CAS  Google Scholar 

  137. Sun Y, Cui F, Shi K, et al. The effect of chitosan molecular weight on the characteristics of spray-dried methotrexate-loaded chitosan microspheres for nasal administration. Drug Dev Ind Pharm 2009 Mar; 35(3): 379–86

    Article  PubMed  CAS  Google Scholar 

  138. Martinac A, Filipovic-Grcic J, Voinovich D, et al. Development and bioadhesive properties of chitosan-ethylcellulose microspheres for nasal delivery. Int J Pharm 2005 Mar 3; 291(1-2): 69–77

    Article  PubMed  CAS  Google Scholar 

  139. Hascicek C, Gonul N, Erk N. Mucoadhesive microspheres containing gentamicin sulfate for nasal administration: preparation and in vitro characterization. Farmaco 2003 Jan; 58(1): 11–6

    Article  PubMed  CAS  Google Scholar 

  140. Kaye RS, Purewal TS, Alpar OH. Development and testing of particulate formulations for the nasal delivery of antibodies. J Control Release 2009 Apr 17; 135(2): 127–35

    Article  PubMed  CAS  Google Scholar 

  141. Sarisozen C, Arica B, Orman MN, et al. Optimization of prednisolone acetate-loaded chitosan microspheres using a 2(3) factorial design for preventing restenosis. Drug Deliv 2010 Apr; 17(3): 178–86

    Article  PubMed  CAS  Google Scholar 

  142. Nagda C, Chotai NP, Patel U, et al. Preparation and characterization of spray-dried mucoadhesive microspheres of aceclofenac. Drug Dev Ind Pharm 2009 Oct; 35(10): 1155–66

    Article  PubMed  CAS  Google Scholar 

  143. Thompson CJ, Hansford D, Higgins S, et al. Preparation and evaluation of microspheres prepared from novel polyester-ibuprofen conjugates blended with non-conjugated ibuprofen. J Microencapsul 2009 Dec; 26(8): 676–83

    Article  PubMed  CAS  Google Scholar 

  144. Luz PP, Neri CR, Serra OA. Dextrin-microencapsulated porphyrin: luminescent properties. Ann N Y Acad Sci 2008; 1130: 91–6

    Article  PubMed  CAS  Google Scholar 

  145. Guerrero S, Muniz E, Teijon C, et al. Ketotifen-loaded microspheres prepared by spray-drying poly(D,L-lactide) and poly(D,L-lactide-co-glycolide) polymers: characterization and in vivo evaluation. J Pharm Sci 2008 Aug; 97(8): 3153–69

    Article  PubMed  CAS  Google Scholar 

  146. Patel P, Mundargi RC, Babu VR, et al. Microencapsulation of doxycycline into poly(lactide-co-glycolide) by spray drying technique: effect of polymer molecular weight on process parameters. J Appl Polym Sci 2008; 108(6): 4038–46

    Article  CAS  Google Scholar 

  147. Blanco MD, Sastre RL, Teijon C, et al. 5-Fluorouracil-loaded microspheres prepared by spray-drying poly(D,L-lactide) and poly(lactide-co-glycolide) polymers: characterization and drug release. J Microencapsul 2005 Sep; 22(6): 671–82

    Article  PubMed  CAS  Google Scholar 

  148. Youan BB. Microencapsulation of superoxide dismutase into biodegradable microparticles by spray-drying. Drug Deliv 2004 May-Jun; 11(3): 209–14

    Article  PubMed  CAS  Google Scholar 

  149. Montanari L, Cilurzo F, Selmin F, et al. Poly(lactide-co-glycolide) micro-spheres containing bupivacaine: comparison between gamma and beta irradiation effects. J Control Release 2003 Jul 31; 90(3): 281–90

    Article  PubMed  CAS  Google Scholar 

  150. Wang FJ, Wang CH. Etanidazole-loaded microspheres fabricated by spray-drying different poly(lactide/glycolide) polymers: effects on microsphere properties. J Biomater Sci Polym Ed 2003; 14(2): 157–83

    Article  PubMed  CAS  Google Scholar 

  151. Blanco-Prieto MJ, Besseghir K, Zerbe O, et al. In vitro and vivo evaluation of a somatostatin analogue released from PLGA microspheres. J Control Release 2000 Jun 15; 67(1): 19–28

    Article  PubMed  CAS  Google Scholar 

  152. Blanco-Prieto MJ, Besseghir K, Orsolini P, et al. Importance of the test medium for the release kinetics of a somatostatin analogue from poly-(D,L-lactide-co-glycolide) microspheres. Int J Pharm 1999 Jul 20; 184(2): 243–50

    Article  PubMed  CAS  Google Scholar 

  153. Castelli F, Conti B, Maccarrone DE, et al. Comparative study of ‘in vitro’ release of anti-inflammatory drugs from polylactide-co-glycolide micro-spheres. Int J Pharm 1998; 176(1): 85–98

    Article  CAS  Google Scholar 

  154. Mi F, Wong T, Shyu S, et al. Chitosan microspheres: modification of polymeric chem-physical properties of spray-dried microspheres to control the release of antibiotic drug. J Appl Polym Sci 1999; 71(5): 747–59

    Article  CAS  Google Scholar 

  155. Kristmundsdóttir T, Gudmundsson ÓS, Ingvarsdóttir K. Release of diltiazem from Eudragit microparticles prepared by spray-drying. Int J Pharm 1996; 137(2): 159–65

    Article  Google Scholar 

  156. Pavanetto F, Genta I, Giunchedi P, et al. Spray-dried albumin microspheres for the intra-articular delivery of dexamethasone. J Microencapsul 1994 Jul–Aug; 11(4): 445–54

    Article  PubMed  CAS  Google Scholar 

  157. Pavanetto F, Genta I, Giunchedi P, et al. Evaluation of spray drying as a method for polylactide and polylactide-co-glycolide microsphere preparation. J Microencapsul 1993 Oct-Dec; 10(4): 487–97

    Article  PubMed  CAS  Google Scholar 

  158. Peek LJ, Middaugh CR, Berkland C. Nanotechnology in vaccine delivery. Adv Drug Deliv Rev 2008 May 22; 60(8): 915–28

    Article  PubMed  CAS  Google Scholar 

  159. Atuah KN, Walter E, Merkle HP, et al. Encapsulation of plasmid DNA in PLGA-stearylamine microspheres: a comparison of solvent evaporation and spray-drying methods. J Microencapsul 2003 May–Jun; 20(3): 387–99

    PubMed  CAS  Google Scholar 

  160. Gayakwad SG, Bejugam NK, Akhavein N, et al. Formulation and in vitro characterization of spray-dried antisense oligonucleotide to NF-kappaB encapsulated albumin microspheres. J Microencapsul 2009 Dec; 26(8): 692–700

    Article  PubMed  CAS  Google Scholar 

  161. Oster CG, Kissel T. Comparative study of DNA encapsulation into PLGA microparticles using modified double emulsion methods and spray drying techniques. J Microencapsul 2005 May; 22(3): 235–44

    Article  PubMed  CAS  Google Scholar 

  162. Kusonwiriyawong C, Atuah K, Alpar OH, et al. Cationic stearylamine-containing biodegradable microparticles for DNA delivery. J Microencapsul 2004 Feb; 21(1): 25–36

    Article  PubMed  CAS  Google Scholar 

  163. Walter E, Dreher D, Kok M, et al. Hydrophilic poly(DL-lactide-co-glycolide) microspheres for the delivery of DNA to human-derived macrophages and dendritic cells. J Control Release 2001 Sep 11; 76(1–2): 149–68

    Article  PubMed  CAS  Google Scholar 

  164. Prinn KB, Costantino HR, Tracy M. Statistical modeling of protein spray drying at the lab scale. AAPS PharmSciTech 2002; 3(1): E4

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Michael Faba for help with constructing chemical structures for figure 3, and Charles Cooney for help with scanning electron microscopy. The research was supported by the Natural Sciences and Engineering Research Council of Canada, and the Way Memorial Trust Award of Queen’s University. The authors have declared no conflicts of interest that are relevant to the content of this review article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ronald J. Neufeld.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bowey, K., Neufeld, R.J. Systemic and Mucosal Delivery of Drugs within Polymeric Microparticles Produced by Spray Drying. BioDrugs 24, 359–377 (2010). https://doi.org/10.2165/11539070-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11539070-000000000-00000

Keywords

Navigation