Advertisement

Nanoencapsulation of water-soluble drug, lamivudine, using a double emulsion spray-drying technique for improving HIV treatment

  • Lesego Tshweu
  • Lebogang Katata
  • Lonji Kalombo
  • Hulda Swai
Research Paper

Abstract

Current treatments available for human immunodeficiency virus, namely antiretrovirals, do not completely eradicate the virus from the body, leading to life-time commitment. Many antiretrovirals suffer drawbacks from toxicity and unpleasant side effects, causing patience non-compliance. To minimize challenges associated with the antiretrovirals, biodegradable nanoparticles used as drug delivery systems hold tremendous potential to enhance patience compliance. The main objective of this work was to load lamivudine (LAM) into poly(epsilon-caprolactone) (PCL) nanoparticles. LAM is a hydrophilic drug with low plasma half-life of 5–7 h and several unpleasant side effects. LAM was nanoencapsulated into PCL polymer via the double emulsion spray-drying method. Formulation parameters such as the effect of solvent, excipient and drug concentration were optimized for the synthesis of the nanoparticles. Spherical nanoparticles with an average size of 215 ± 3 nm and polydispersity index (PDI) of 0.227 ± 0.01 were obtained, when ethyl acetate and lactose were used in the preparation. However, dichloromethane presented sizes larger than 454 ± 11 nm with PDI of more than 0.4 ± 0.05, irrespective of whether lactose or trehalose was used in the preparation. Some of the nanoparticles prepared with trehalose resulted in crystal formation. UV spectroscopy showed encapsulation efficiency ranging from 68 ± 4 to 78 ± 4 % for LAM depending on the starting drug concentration. Fourier transform infrared spectroscopy and X-ray diffraction confirmed the possibility of preparing amorphous PCL nanoparticles containing LAM. Drug release extended for 4 days in pH 1.3, pH 4.5 and pH 6.8. These results indicated that LAM-loaded PCL nanoparticles show promise for controlled delivery.

Keywords

Spray-dried Poly(epsilon-caprolactone) Lamivudine Nanoparticles Double emulsion Nanomedicine 

Notes

Acknowledgments

The authors would like to thank South African National Research Foundation for providing financial support for the manuscript presented. Thomas Malwela is acknowledged for the SEM analysis of the nanoparticles.

Supplementary material

11051_2013_2040_MOESM1_ESM.docx (261 kb)
Supplementary material 1 (DOCX 261 kb)

References

  1. Arpagaus C, Meuri M (2010) Laboratory scale spray drying of inhalable particles: a review, Respir Drug Deliv VCU: 469–473 Google Scholar
  2. Baras B, Benoit MA, Gillard J (2000) Influence of various technological parameters on the preparation of spray-dried poly (ε-caprolactone) microparticles containing a model antigen. J Microencapsul 17(4):485–498CrossRefGoogle Scholar
  3. Broadhead J, Rouan SKE, Rhodes CT (1992) The spray drying of pharmaceuticals. Drug Dev Ind Pharm 18:1169–1206CrossRefGoogle Scholar
  4. Caroline MP, Faulds D (1997) Lamivudine: a review of its antiretroviral activity. Pharmacokinetic property and therapeutic efficiency in management of HIV infection. Drugs 53:7–680Google Scholar
  5. Chernysheva YV, Babak VG, Kildeeva NR, Boury, Benoil F (2003) Effect of the type of hydrophobic polymers on the size of nanoparticles obtained by emulsification–solvent evaporation. Mendeleev Commun 13(2):65–67Google Scholar
  6. Clercq ED (2009) Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV. Int J Antimicrob Agents 33:307–320Google Scholar
  7. das Neves J, Amiji MM, Bahia MF, Sarmento B (2010) Nanotechnology-based systems for the treatment and prevention of HIV/AIDS. Adv Drug Deliv Rev 62:458–477Google Scholar
  8. Dash TK, Konkimalla VB (2012) Poly-є-caprolactone based formulations for drug delivery and tissue engineering: a review. J Control Rel 158:15–33Google Scholar
  9. Dash S, Ng WK, Kanaujia P, Kim S, Tan RBH (2012) Formulation design, preparation and physicochemical characterizations of solid lipid nanoparticles containing a hydrophobic drug: effects of process variables. Colloids Surf B: Biointerf 88:483–489Google Scholar
  10. Dev A, Binulal NS, Anitha A, Nair SV, Furuike T, Tamura H, Jayakumar R (2010) Preparation of poly(lactic acid)/chitosan nanoparticles for anti-HIV drug. Carbohydr Polym 80:833–838CrossRefGoogle Scholar
  11. Gupta U, Jain NK (2010) Non-polymeric nano-carriers in HIV/AIDS drug deliveryand targeting. Adv Drug Deliv Rev 62:478–490CrossRefGoogle Scholar
  12. Higashiyama T (2002) Novel fuctions and applications of trehalose. Pure Appl Chem 74(7):1263–1269Google Scholar
  13. Inez MV, Kersten G, Marjan MF, Beuvery C, Verhoef JC, Junginger HE (2003) Chitosan microparticles for mucosal vaccination against diphtheria:oral and nasal efficacy studies in mice. Vaccine 21:13–14Google Scholar
  14. Jozwiakowski MJ, Nguyen NT, SiscoI JM, Spancake CW (1996) Solubility behaviour of Lamivudine crystal forms in recrystallization solvents. J Pharm Sci 85:193–199CrossRefGoogle Scholar
  15. Jyothi NVN, Prasanna PM, Sakarkar SN, Prabha KS, Ramaiah PS, Srawan, Srawan GY (2010) Microencapsulation techniques, factors influencing encapsulation efficiency. J Microencapsul 27(3):187–197CrossRefGoogle Scholar
  16. Kao JH, Wu NH, Chen PJ, Lai MY, Chen DS (2000) Hepatitis B genotype and response to interferon therapy. J Hepatol 33:998–1002CrossRefGoogle Scholar
  17. Katata L, Tshweu L, Naidoo S, Kalombo L, Swai H (2012) Design and formulation of nano-sized spray dried Efavirenz-Part I: influence of formulation parameters. J Nanopart Res 14:1247CrossRefGoogle Scholar
  18. Kho K, Cheow WS, Lie RH, Hadinoto K (2010) Aqueous re-dispersibility of spray-dried antibiotic-loaded polycaprolactone nanoparticles aggregate for inhaled anti-biofilm therapy. Powder Technol 203:432–439CrossRefGoogle Scholar
  19. Kumari A, Yadav SK, Yadav SC (2010) Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B 75:1–18CrossRefGoogle Scholar
  20. Look M, Bandyopadhyay A, Blum JS, Fahmy JM (2010) Application of nanotechnologies for improved immune response against infectious diseases in the developing world. Adv Drug Deliv Rev 62:378–393CrossRefGoogle Scholar
  21. Luong-Van E, Grondahl L, Nurcombe V, Cool S (2007) In vitro biocompatibility and bioactivity of microencapsulated heparan sulfate. Biomaterials 28:2127–2136CrossRefGoogle Scholar
  22. Maia J, Santana M (2004) The effect of some processing conditions on the characteristics of biodegradable microspheres obtained by an emulsion solvent evaporation process. Braz J Chem Eng 21:1–12Google Scholar
  23. Mishra B, Patel BB, Tiwari S (2010) Colloidal nanocarriers: a review on formulation technology, types and application torward targeted drug delivery. Nanomed: Nanotechnol Biol Med 6:9–24Google Scholar
  24. Mourya V, Inamdar N (2008) Chitosan-modifications and applications: opportunities galore. J React Funct Polymers 68:1013–1051Google Scholar
  25. Proikalis CS, Tarantalli PA, Andreopoulos AG (2006) The role of polymer/drug interactions on the sustained release from poly (DL -lactic acid) tablets. Eur Polymer J 42:3269–3276CrossRefGoogle Scholar
  26. Rao KS, Ghorpade A, Labhasetwar V (2009) Targeting anti-HIV drugs to the CNS. Expert Opin Drug Deliv 6(8):771–784CrossRefGoogle Scholar
  27. Rathbun, R C & Greenfield, R A (2011) Antiretroviral Therapy for HIV Infection. Available: http://emedicine.medscape.com/article/1533218-overview [Accessed 08/11/2011]
  28. Roser B (1991) Trehalose drying-A novel replacement for freeze-drying. Biopharm 4:47–52Google Scholar
  29. Sahoo S, Sasmal A, Nanda R, Phani AR, Nayak PL (2010) Synthesis of chitosan-polycaprolactone blend for control delivery of ofloxacin drug. Carbohydr Polym 79:106–113CrossRefGoogle Scholar
  30. Semete B, Booysen L, Lemmer Y, Kalombo L, Katata L, Verschoor J, Swai H (2010) In vivo evaluation of the biodistribution and safety of PLGA nanoparticles as drug delivery systems. Nanomedicine: nanotechnology. Biol Med 6:662–671Google Scholar
  31. Shin IG, Kim SY, Lee YM, Cho CS, Sung YK (1998) Methoxypoly (ethylene glycol)/E-caprolactone amphiphilic block copolymeric micellecontaining indomethacin: I. Preparation and characterization. J Control Release 51:1–11Google Scholar
  32. Simperler A, Kornherr A, Chopra R, Bonnet PA, Jones W, Motherwell WDS, Zifferer G (2006) Glass transition temperature of glucose, sucrose, and trehalose: an experimental and in silico study. J Phys Chem B 110:19678–19684Google Scholar
  33. Song KC, Lee HS, Choung IY, Cho KI, Ahn Y, Choi EJ (2006) The effect of type of organic phase solvents on the particle size of poly(D, L-lactide-co-glycolide) nanoparticles. Colloids Surf A: Physicochem Eng Aspects 276:162–167CrossRefGoogle Scholar
  34. Takeuchi H, Yasuji T, Hino T, Yamamoto H, Kawashima Y (1998) Spray-dried composite particles of lactose and sodium alginate for direct tableting and controlled releasing. Int J Pharm 174:91–100CrossRefGoogle Scholar
  35. Wong HL, Chattopadhyay N, Wu XY, Bendayan R (2010) Nanotechnology applications for improved delivery of antiretroviral drugs to the brain. Adv Drug Deliv Rev 62:503–517Google Scholar
  36. Woodruff MA, Hutmacher DW (2010) The return of a forgotten polymer—Polycaprolactone in the 21st century. Prog Polym Sci 35:1217–1256CrossRefGoogle Scholar
  37. Wu CS (2005) A comparison of the structure, thermal properties, and biodegradability of polycaprolactone/chitosan and acrylic acid grafted polycaprolactone/chitosan. Polymer 46:147–155CrossRefGoogle Scholar
  38. Young RJ, Lovell PA (1991) Introduction to polymers, 2nd edn. CRC Press, BocaRaton, New York, Washington, DC, pp 265–266CrossRefGoogle Scholar
  39. Zhao Y, Fu J, Dennis KPN, Wu C (2004) Formation and degradation of poly(D, L-lactide) nanoparticles and their potential application as controllable releasing devices. Macromol Biosci 4:901–906CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Lesego Tshweu
    • 1
  • Lebogang Katata
    • 2
  • Lonji Kalombo
    • 1
  • Hulda Swai
    • 1
  1. 1.Materials Science and Manufacturing, Polymers and CompositesCouncil for Scientific and Industrial ResearchPretoriaSouth Africa
  2. 2.Chemistry Department, Faculty of Agriculture, Science and TechnologyNorth West UniversityMmabathoSouth Africa

Personalised recommendations