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Mechanisms of drug release from advanced drug formulations such as polymeric-based drug-delivery systems and lipid nanoparticles

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Abstract

Drug release from a polymeric nanocarrier is affected by several factors including the sort of composition (drug, polymer, and excipient), the ratio of composition, physical or chemical interaction between components, and manufacturing methods. Depending on the mechanism of drug release from the vehicles, it can be divided into four categories (diffusion, solvent, chemical interaction, and stimulated release). Recently, lipids have attracted great interest as carriers for water-insoluble drug delivery. Lipid-based drug-delivery systems have received a lot of interest because of their ability to improve solubility and bioavailability of drugs that are poorly soluble in water. The lipid carrier, formulation strategy, and rational drug-delivery system should be selected appropriately for a lipid-based drug-delivery system to be successful. In this review, the general release characteristics and mechanisms of drug from nanocarriers will be discussed.

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References

  • Abouelmagd SA, Hyun H, Yeo Y (2014) Extracellularly activatable nanocarriers for drug delivery to tumors. Expert Opin Drug Deliv 11:1601–1618

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Acharya S, Sahoo SK (2011) PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect. Adv Drug Deliv Rev 63:170–183

    Article  CAS  PubMed  Google Scholar 

  • Agrawal S, Giri TK, Tripathi DK, Alexander AA (2012) A review on novel therapeutics strategies for the enhancement of solubility for hydrophobic drugs through lipid and surfactant based self micro emulsifying drug delivery system: a novel approach. Am J Drug Discov Dev 2:143–183

    Article  CAS  Google Scholar 

  • Amidon GL, Lennernas H, Shah VP, Crison JR (1995) A theoretical basis for a biopharmaceutic drug classification: the correlation in vitro drug product dissolution and in vivo bioavailability. Pharm Res 12:413–420

    Article  CAS  PubMed  Google Scholar 

  • Aungst BJ (1993) Novel formulation strategies for improving oral bioavailability of drugs with poor membrane permeation or pre-systemic metabolism. J Pharm Sci 82:979–987

    Article  CAS  PubMed  Google Scholar 

  • Bajpai AK, Shukla SK, Bhanu S, Kankane S (2008) Responsive polymers in controlled drug delivery. Prog Polym Sci 33:1088–1118

    Article  CAS  Google Scholar 

  • Brannon-Peppas L, Blanchette JO (2004) Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliv Rev 56:1649–1659

    Article  CAS  PubMed  Google Scholar 

  • Burkersroda FV, Schedl L, Göpferich A (2002) Why degradable polymers undergo surface erosion or bulk erosion. Biomaterials 23:4221–4231

    Article  Google Scholar 

  • Cauchetier E, Deniau M, Fessi H, Astier A, Paul M (2003) Atovaquone-loaded nanocapsules: influence of the nature of the polymer on their in vitro characteristics. Int J Pharm 250:273–281

    Article  CAS  PubMed  Google Scholar 

  • Chang C, Wei H, Quan CY, Li YY, Liu J, Wang ZC, Cheng SX, Zhang XZ, Zhuo RX (2008) Fabrication of thermosensitive PCL-PNIPAAm-PCL triblock copolymeric micelles for drug delivery. J Polym Sci Part A 46:3048–3057

    Article  CAS  Google Scholar 

  • Costa P, Sousa Lobo JM (2001) Modeling and comparison of dissolution profiles. Eur J Pharm Sci 13:123–133

    Article  CAS  PubMed  Google Scholar 

  • Craig DQM, Baker SA, Banning D, Booth SW (1995) An investigation into the mechanisms of self-emulsification using particle size analysis and low frequency dielectric spectroscopy. Int J Pharm 114:103–110

    Article  CAS  Google Scholar 

  • Crank J (1975) The mathematics of diffusion. Clarendon Press, Oxford

    Google Scholar 

  • Csuhai E, Kangarlou S, Xiang TX, Ponta A, Bummer P, Choi D, Anderson BD (2015) Determination of key parameters for a mechanism-based model to predict Doxorubicin release from actively loaded liposomes. J Pharm Sci 104:1087–1098

    Article  CAS  PubMed  Google Scholar 

  • Dahan A, Hoffman A (2008) Rationalizing the selection of oral lipid based drug delivery systems by an in vitro dynamic lipolysis model for improved oral bioavailability of poorly water soluble drugs. J Control Release 129:1–10

    Article  CAS  PubMed  Google Scholar 

  • Dash S, Murthy PN, Nath L, Chowdhury P (2010) Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm 67:217–223

    CAS  PubMed  Google Scholar 

  • Fang JY, Fang CL, Liu CH, Su YH (2008) Lipid nanoparticles as vehicles for topical psoralen delivery: solid lipid nanoparticles (SLN) versus nanostructured lipid carriers (NLC). Eur J Pharm Biopharm 70:633–640

    Article  CAS  PubMed  Google Scholar 

  • Farah N, Denis J (2001) Orally administrable composition capable of providing enhanced bioavailability when ingested. US Patent 6 ,312,704

  • Fattal E, Rojas J, Roblot-Treupel L, Andremont A, Couvreur P (1991) Ampicillin-loaded liposomes and nanoparticles: comparison of drug loading, drug release and in vitro antimicrobial activity. J Microencapsulation 8:29–36

    Article  CAS  PubMed  Google Scholar 

  • Folkman J, Long DM (1964) The use of silicone rubber as a carrier for prolonged drug therapy. J Surg Res 4:139–142

    Article  CAS  PubMed  Google Scholar 

  • Freiberg S, Zhu XX (2004) Polymer microspheres for controlled drug release. Int J Pharm 282:1–18

    Article  PubMed  Google Scholar 

  • Fugit KD, Anderson BD (2014) Dynamic, nonsink method for the simultaneous determination of drug permeability and binding coefficients in liposomes. Mol Pharm 11:1314–1325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fugit KD, Xiang TX, Choi DH, Kangarlou S, Csuhai E, Bummer PM, Anderson BD (2015) Mechanistic model and analysis of doxorubicin release from liposomal formulations. J Control Release 217:82–91

    Article  CAS  PubMed  Google Scholar 

  • Gursoy RN, Benita S (2004) Self-emulsifying drug delivery systems (SMEDDS) for improved oral delivery of lipophilic drugs. Biomed Pharmacother 58:173–182

    Article  PubMed  Google Scholar 

  • Hayashi T, Kanbe H, Okada M, Suzuki M, Ikeda Y, Onuki Y, Kaneko T, Sonobe T (2005) Formulation study and drug release mechanism of a new theophylline sustained-release preparation. Int J Pharm 304:91–101

    Article  CAS  PubMed  Google Scholar 

  • Higuchi T (1963) Mechanism of sustained-action medication. Theoretical analysis of release of solid drug dispersed in solid matrices. J Pharm Sci 52:1145–1149

    Article  CAS  PubMed  Google Scholar 

  • Jain A, Jain SK (2016) Stimuli-responsive smart liposomes in cancer targeting. Curr Drug Targets. doi:10.2174/1389450117666160208144143

    PubMed  Google Scholar 

  • Jannin V, Musakhanian J, Marchaud D (2008) Approaches for the development of solid and semi-solid lipid-based formulations. Adv Drug Deliv Rev 60:734–746

    Article  CAS  PubMed  Google Scholar 

  • Kaity S, Isaac J, Ghosh A (2013) Interpenetrating polymer network of locust bean gum-poly (vinyl alcohol) for controlled release drug delivery. Carbohydr Polym 94:456–467

    Article  CAS  PubMed  Google Scholar 

  • Knepp VM, Hinz RS, Szoka FC, Guy RH (1987) Controlled drug release from a novel liposomal delivery system. I. Investigation of transdermal potential. J Control Release 5:211–221

    Article  Google Scholar 

  • Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA (1983) Mechanisms of potassium chloride release from compressed, hydrophilic, polymeric matrices: effect of entrapped air. J Pharm Sci 72:1189–1191

    Article  CAS  PubMed  Google Scholar 

  • Langer R, Peppas N (2006) Chemical and physical structure of polymers as carriers for controlled release of bioactive agents: a review. J Macromol Sci 23:61–126

    Article  Google Scholar 

  • Lee PI (1984) Novel approach to zero-order drug delivery via immobilized nonuniform drug distribution in glass hydrogels. J Pharm Sci 73:1344–1347

    Article  CAS  PubMed  Google Scholar 

  • Lee WC, Chu IM (2008) Preparation and degradation behavior of polyanhydrides nanoparticles. J Biomed Mater Res B 84:138–146

    Article  Google Scholar 

  • Lee JH, Yeo Y (2015) Controlled drug release from pharmaceutical nanocarriers. Chem Eng Sci 125:75–84

    Article  CAS  PubMed  Google Scholar 

  • Lee SH, Mok H, Lee Y, Park TG (2011) Self-assembled siRNA–PLGA conjugate micelles for gene silencing. J Control Release 152:152–158

    Article  CAS  PubMed  Google Scholar 

  • Li W, Li J, Gao J, Li B, Xia Y, Meng Y, Yu Y, Chen H, Dai J, Wang H, Guo Y (2011) The fine-tuning of thermosensitive and degradable polymer micelles for enhancing intracellular uptake and drug release in tumors. Biomaterials 32:3832–3844

    Article  CAS  PubMed  Google Scholar 

  • Lin CC, Metters AT (2006) Hydrogels in controlled release formulations: network design and mathematical modeling. Adv Drug Deliv Rev 58:1379–1408

    Article  CAS  PubMed  Google Scholar 

  • Lu Y, Low PS (2002) Folate-mediated delivery of macromolecular anticancer therapeutic agents. Adv Drug Deliv Rev 54:675–693

    Article  CAS  PubMed  Google Scholar 

  • Maeda H, Nakamura H, Fang J (2013) The EPR effect for macromolecular drug delivery to solid tumors: improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv Drug Deliv Rev 65:71–79

    Article  CAS  PubMed  Google Scholar 

  • Mahesh D, Mandan J, Banode S (2001) Emulsion based drug delivery system. Indian J Nov Drug Deliv 3:2–8

    Google Scholar 

  • Mehnert W, Mäder K (2001) Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliv Rev 47:165–196

    Article  CAS  PubMed  Google Scholar 

  • Middleton JC, Tipton AJ (2000) Synthetic biodegradable polymers as orthopedic devices. Biomaterials 21:2335–2346

    Article  CAS  PubMed  Google Scholar 

  • Min KH, Kim JH, Bae SM, Shin H, Kim MS, Park S, Lee H, Park RW, Kim IS, Kim K, Kwon IC, Jeong SY, Lee DS (2010) Tumoral acidic pH- responsive MPEG-poly(β-amino ester)polymeric micelles for cancer targeting therapy. J Control Release 144:259–266

    Article  CAS  PubMed  Google Scholar 

  • Muller RH, Mader K, Gohla S (2000) Solid lipid nanoparticles (SLN) for controlled drug delivery—a review of the state of the art. Eur J Pharm Biopharm 50:161–177

    Article  CAS  PubMed  Google Scholar 

  • Muller RH, Radtke M, Wissing SA (2002) Soli lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Deliv Rev 54:S131–S155

    Article  CAS  PubMed  Google Scholar 

  • O’driscoll CM, Griffin BT (2008) Biopharmaceutical challenges associated with drugs with low aqueous solubility-the potential impact of lipid-based formulations. Adv Drug Deliv Rev 60:617–624

    Article  PubMed  Google Scholar 

  • Patel PV, Desai RT, Kapupara PP (2010) Self emulsifying drug delivery system: a conventional and alternative approach to improve oral bioavailability of lipophilic drugs. J Drug Dev Res 2:9344–9375

    Google Scholar 

  • Peppas NA, Bures P, Leobandung W, Ichikawa H (2000) Hydrogels in pharmaceutical formulations. Eur J Pharm Biopharm 50:27–46

    Article  CAS  PubMed  Google Scholar 

  • Pouton CW (2000) Lipid formulations for oral administration of drugs nanoemulsifying, self-emulsifying and self-microemulsifying drug delivery systems. Eur J Pharm Sci 11:S93–S98

    Article  CAS  PubMed  Google Scholar 

  • Pouton CW (2006) Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. Eur J Pharm Sci 29:278–287

    Article  CAS  PubMed  Google Scholar 

  • Prabaharan M, Grailer JJ, Pilla S, Steeber DA, Gong S (2009) Amphiphilic multi-arm-block copolymer conjugated with doxorubicin via pH-sensitive hydrazone bond for tumor-targeted drug delivery. Biomaterials 30:5757–5766

    Article  CAS  PubMed  Google Scholar 

  • Rajput DS, Alexander A, Jain V, Giri TK, Tripathi DK, Ajazuddin (2012) Novel integrated approach for the strategic delivery of hydrophobic drugs by the use of self emulsifying drug delivery system. J Appl Sci 12(6):502–517

    Article  CAS  Google Scholar 

  • Ritger PL, Peppas NA (1987) A simple equation for description of solute release II. Fickian and anomalous release from swellable devices. J Control Release 5:37–42

    Article  CAS  Google Scholar 

  • Sarpietro MG, Castelli F (2011) Transfer kinetics from colloidal drug carriers and liposomes to biomembrane models: DSC studies. J Pharm Bioall Sci 3:77–88

    Article  CAS  Google Scholar 

  • Sarpietro MG, Accolla ML, Celia C, Grattoni A, Castelli F, Fresta M, Ferrari M, Paolino D (2013) Differential scanning calorimetry as a tool to investigate the transfer of anticancer drugs to biomembrane model. Curr Drug Targets 14:1053–1060

    Article  CAS  PubMed  Google Scholar 

  • Schaefer JJ, Ma C, Harris JM (2012) Confocal Raman microscopy probing of temperature-controlled release from individual, optically-trapped phospholipid vesicles. Anal Chem 84:9505–9512

    Article  CAS  PubMed  Google Scholar 

  • Schwarz C (1995) Lipidnanopartikel: herstellung, charakterisierung, arzneistoffinkorporation and freisetzung, sterilization und lyophilisation. Ph.D. thesis, Free University of Berlin

  • Siegel RA, Rathbone MJ (2012) Overview of controlled release mechanisms. In: Siepmann J et al (eds) Fundamentals and applications of controlled release drug delivery. Advances in delivery science and technology. Springer, New York, pp 21–22

    Google Scholar 

  • Siepmann J, Peppas NA (2001) Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). Adv Drug Deliv Rev 48:139–157

    Article  CAS  PubMed  Google Scholar 

  • Small EF, Dan NR, Wrenn SP (2012) Low-frequency ultrasound-induced transport across non-raft-forming ternary lipid bilayers. Langmuir 28:14364–14372

    Article  CAS  PubMed  Google Scholar 

  • Sobko AA, Kovalchuk SI, Kotova EA, Antonenko YN (2010) Induction of lipid flip-flop colicin E1—a hallmark of proteolipidic pore formation in liposome membranes. BioChemistry 75:728–733

    CAS  PubMed  Google Scholar 

  • Talelli M, Iman M, Varkouhi AK, Rijcken CJF, Schiffelers RM, Etrych T, Ulbrich, K, van Nostrum CF, Lammers T, Storm G, Hennink WE (2010) Core-cross linked polymeric micelles with controlled release of covalently entrapped doxorubicin. Biomaterials 31:7797–7804

    Article  CAS  PubMed  Google Scholar 

  • Torchilin VP, Lukyanov AN (2003) Peptide and protein drug delivery to and into tumors: challenges and solutions. Drug Discov Today 8:259–266

    Article  CAS  PubMed  Google Scholar 

  • Wei Y, Guo J, Zheng X, Wu J, Zhou Y, Yu Y, Ye Y, Zhang L, Zhao L (2014) Preparation, pharmacokinetics and biodistribution of baicalin-loaded liposomes. Int J Nanomedicine 9:3623–3630

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xu S, Olenyuk BZ, Okamoto CT, Hamm-Alvarez SF (2013) Targeting receptor-mediated endocytotic pathways with nanoparticles: rationale and advances. Adv Drug Deliv Rev 65:121–138

    Article  CAS  PubMed  Google Scholar 

  • Yoo HS, Park TG (2001) Biodegradable polymeric micelles composed of doxorubicin conjugated PLGA–PEG blockcopolymer. J Control Release 70:63–70

    Article  CAS  PubMed  Google Scholar 

  • Zeng L, An L, Wu X (2011) Modeling drug-carrier interaction in the drug release from nanocarriers. J Drug Deliv. doi: 10.1155/2011/370308

    PubMed  PubMed Central  Google Scholar 

  • Zhuang CY, Li N, Wang M, Zhang XN, Pan WS, Peng JJ, Pan YS, Tang X (2010) Preparation and characterization of vinpocetine loaded nanostructured lipid carriers (NLC) for improved oral bioavailability. Int J Pharm 394:179–185

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the Basic Science Research Program (2016R1A2B4011294) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology.

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Correspondence to Beom-Jin Lee or Cheong-Weon Cho.

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Son, GH., Lee, BJ. & Cho, CW. Mechanisms of drug release from advanced drug formulations such as polymeric-based drug-delivery systems and lipid nanoparticles. Journal of Pharmaceutical Investigation 47, 287–296 (2017). https://doi.org/10.1007/s40005-017-0320-1

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