Skip to main content

Advertisement

SpringerLink
Log in

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

  • Research Paper
  • Published:
Journal of Nanoparticle Research Aims and scope Submit manuscript

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.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Arpagaus C, Meuri M (2010) Laboratory scale spray drying of inhalable particles: a review, Respir Drug Deliv VCU: 469–473

  • 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):485–498

    Article  CAS  Google Scholar 

  • Broadhead J, Rouan SKE, Rhodes CT (1992) The spray drying of pharmaceuticals. Drug Dev Ind Pharm 18:1169–1206

    Article  CAS  Google Scholar 

  • Caroline MP, Faulds D (1997) Lamivudine: a review of its antiretroviral activity. Pharmacokinetic property and therapeutic efficiency in management of HIV infection. Drugs 53:7–680

    Google Scholar 

  • 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):65–67

  • Clercq ED (2009) Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV. Int J Antimicrob Agents 33:307–320

    Google Scholar 

  • 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 62:458–477

    Google Scholar 

  • Dash TK, Konkimalla VB (2012) Poly-є-caprolactone based formulations for drug delivery and tissue engineering: a review. J Control Rel 158:15–33

    Google Scholar 

  • 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 88:483–489

    Google Scholar 

  • 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 80:833–838

    Article  CAS  Google Scholar 

  • Gupta U, Jain NK (2010) Non-polymeric nano-carriers in HIV/AIDS drug deliveryand targeting. Adv Drug Deliv Rev 62:478–490

    Article  CAS  Google Scholar 

  • Higashiyama T (2002) Novel fuctions and applications of trehalose. Pure Appl Chem 74(7):1263–1269

    Google Scholar 

  • 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 21:13–14

    Google Scholar 

  • Jozwiakowski MJ, Nguyen NT, SiscoI JM, Spancake CW (1996) Solubility behaviour of Lamivudine crystal forms in recrystallization solvents. J Pharm Sci 85:193–199

    Article  CAS  Google Scholar 

  • Jyothi NVN, Prasanna PM, Sakarkar SN, Prabha KS, Ramaiah PS, Srawan, Srawan GY (2010) Microencapsulation techniques, factors influencing encapsulation efficiency. J Microencapsul 27(3):187–197

    Article  CAS  Google Scholar 

  • Kao JH, Wu NH, Chen PJ, Lai MY, Chen DS (2000) Hepatitis B genotype and response to interferon therapy. J Hepatol 33:998–1002

    Article  CAS  Google Scholar 

  • 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 14:1247

    Article  Google Scholar 

  • 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 203:432–439

    Article  CAS  Google Scholar 

  • Kumari A, Yadav SK, Yadav SC (2010) Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B 75:1–18

    Article  CAS  Google Scholar 

  • 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 62:378–393

    Article  CAS  Google Scholar 

  • Luong-Van E, Grondahl L, Nurcombe V, Cool S (2007) In vitro biocompatibility and bioactivity of microencapsulated heparan sulfate. Biomaterials 28:2127–2136

    Article  CAS  Google Scholar 

  • 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 21:1–12

    Google Scholar 

  • 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 6:9–24

    Google Scholar 

  • Mourya V, Inamdar N (2008) Chitosan-modifications and applications: opportunities galore. J React Funct Polymers 68:1013–1051

    Google Scholar 

  • 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 42:3269–3276

    Article  Google Scholar 

  • Rao KS, Ghorpade A, Labhasetwar V (2009) Targeting anti-HIV drugs to the CNS. Expert Opin Drug Deliv 6(8):771–784

    Article  CAS  Google Scholar 

  • Rathbun, R C & Greenfield, R A (2011) Antiretroviral Therapy for HIV Infection. Available: http://emedicine.medscape.com/article/1533218-overview [Accessed 08/11/2011]

  • Roser B (1991) Trehalose drying-A novel replacement for freeze-drying. Biopharm 4:47–52

    Google Scholar 

  • Sahoo S, Sasmal A, Nanda R, Phani AR, Nayak PL (2010) Synthesis of chitosan-polycaprolactone blend for control delivery of ofloxacin drug. Carbohydr Polym 79:106–113

    Article  CAS  Google Scholar 

  • 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 6:662–671

    Google Scholar 

  • 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 51:1–11

    Google Scholar 

  • 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 110:19678–19684

    Google Scholar 

  • 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 276:162–167

    Article  CAS  Google Scholar 

  • 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 174:91–100

    Article  CAS  Google Scholar 

  • Wong HL, Chattopadhyay N, Wu XY, Bendayan R (2010) Nanotechnology applications for improved delivery of antiretroviral drugs to the brain. Adv Drug Deliv Rev 62:503–517

    Google Scholar 

  • Woodruff MA, Hutmacher DW (2010) The return of a forgotten polymer—Polycaprolactone in the 21st century. Prog Polym Sci 35:1217–1256

    Article  CAS  Google Scholar 

  • Wu CS (2005) A comparison of the structure, thermal properties, and biodegradability of polycaprolactone/chitosan and acrylic acid grafted polycaprolactone/chitosan. Polymer 46:147–155

    Article  CAS  Google Scholar 

  • Young RJ, Lovell PA (1991) Introduction to polymers, 2nd edn. CRC Press, BocaRaton, New York, Washington, DC, pp 265–266

    Book  Google Scholar 

  • 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 4:901–906

    Article  CAS  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Materials Science and Manufacturing, Polymers and Composites, Council for Scientific and Industrial Research, PO Box 395, Meiring Naude Road, Brummeria, Pretoria, 0001, South Africa

    Lesego Tshweu, Lonji Kalombo & Hulda Swai

  2. Chemistry Department, Faculty of Agriculture, Science and Technology, North West University, Mafikeng Campus, Private Bag X2046, Mmabatho, 2735, South Africa

    Lebogang Katata

Authors
  1. Lesego Tshweu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lebogang Katata
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lonji Kalombo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hulda Swai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lesego Tshweu.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 261 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tshweu, L., Katata, L., Kalombo, L. et al. Nanoencapsulation of water-soluble drug, lamivudine, using a double emulsion spray-drying technique for improving HIV treatment. J Nanopart Res 15, 2040 (2013). https://doi.org/10.1007/s11051-013-2040-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11051-013-2040-4

Keywords

Search

Navigation