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Recent Patents on Nanotechnology

Editor-in-Chief

ISSN (Print): 1872-2105
ISSN (Online): 2212-4020

Review Article

Recent Advances in Drug Delivery Strategies for Improved Therapeutic Efficacy of Efavirenz

Author(s): Mitali Patel, Ruhi Shah and Krutika Sawant*

Volume 14, Issue 2, 2020

Page: [119 - 127] Pages: 9

DOI: 10.2174/1872210513666191019103129

Price: $65

Abstract

Background: Efavirenz, an anti-HIV agent, has a noticeable place in the HAART regimen for the treatment and maintenance therapy of AIDS. However, its poor water solubility accounts for hindered absorption and bio-distribution upon administration. This results in its low and variable bioavailability. To circumvent these limitations, various novel formulations of Efavirenz have been investigated in order to mitigate its drawbacks and draw out its maximum therapeutic effect.

Methods: Numerous formulations explored to overcome the drawbacks of Efavirenz include modified/ controlled-release tablets, solid dispersions, polymeric nanoparticles, dendrimers, surface-engineered nanoparticles and various other nanoformulations. Moreover, combinatorial formulations of Efavirenz with other Anti-HIV drugs have also been reported to overcome the problem of Drug-Resistance.

Results: The nanoformulation based strategies, owing to their ability to provide controlled release profile and targeted drug delivery were found to augment bioavailability, therapeutic efficacy and reduce the side effects of the Efavirenz.

Conclusion: This review pivots around the challenges and recent advances in the delivery of Efavirenz with particular emphasis on novel formulations including its patents.

Keywords: Controlled drug delivery system, dendrimers, efavirenz, nanoformulations, targeted delivery, patents.

Graphical Abstract

[1]
Chiappetta DA, Facorro G, de Celis ER, Sosnik A. Synergistic encapsulation of the anti-HIV agent efavirenz within mixed poloxamine/poloxamer polymeric micelles. Nanomedicine (Lond) 2011; 7(5): 624-37.
[http://dx.doi.org/10.1016/j.nano.2011.01.017 PMID: 21371572]
[2]
Okoye AA, Picker LJ. CD4(+) T-cell depletion in HIV infection: Mechanisms of immunological failure. Immunol Rev 2013; 254(1): 54-64.
[http://dx.doi.org/10.1111/imr.12066 PMID: 23772614]
[3]
Gaida R, Truter I, Grobler C. Efavirenz: A review of the epidemiology, severity and management of neuropsychiatric side-effects. SAJP-S Afr J Psychi 2015; 21(3): 94-7.
[http://dx.doi.org/10.4102/sajpsychiatry.v21i3.783]
[4]
Patel GV, Patel VB, Pathak A, Rajput SJ. Nanosuspension of efavirenz for improved oral bioavailability: Formulation optimization, in vitro, in situ and in vivo evaluation. Drug Dev Ind Pharm 2014; 40(1): 80-91.
[http://dx.doi.org/10.3109/03639045.2012.746362 PMID: 23323843]
[5]
Pau AK, George JM. Antiretroviral therapy: Current drugs. Infect Dis Clin North Am 2014; 28(3): 371-402.
[http://dx.doi.org/10.1016/j.idc.2014.06.001 PMID: 25151562]
[6]
Best BM, Goicoechea M. Efavirenz-still first-line king? Expert Opin Drug Metab Toxicol 2008; 4(7): 965-72.
[http://dx.doi.org/10.1517/17425255.4.7.965 PMID: 18624683]
[7]
Tripathi KD. Essentials of medical pharmacology. Jaypee Brothers new delhi, 2004.
[8]
Sweetman SC. Martindale: The complete drug reference. 36th ed. Pharmaceutical Press London 2009.
[9]
Sluis-Cremer N, Tachedjian G. Mechanisms of inhibition of HIV replication by non-nucleoside reverse transcriptase inhibitors. Virus Res 2008; 134(1-2): 147-56.
[http://dx.doi.org/10.1016/j.virusres.2008.01.002 PMID: 18372072]
[10]
Babu GS, Kumar DV, Balakrishna G, Naik RR, Malathy PS. Development and in-vitro evaluation of immediate release tablets of efavirenz. Int J Pharm Biol Chem Sci 2014; 3(3): 56-65.
[11]
Chowdary KPR, Enturi V. Enhancement of dissolution rate and formulation development of efavirenz tablets employing starch phosphate a new modified starch. Int J Pharm Sci Drug Res 2011; 3(2): 80-3.
[12]
Sathigari S, Chadha G, Lee YHP, et al. Physicochemical characterization of efavirenz-cyclodextrin inclusion complexes. AAPS PharmSciTech 2009; 10(1): 81-7.
[http://dx.doi.org/10.1208/s12249-008-9180-3 PMID: 19148759]
[13]
Chowdary KPR, Naresh A. Formulation development of efavirenz tablets employing β cyclodextrin- PVP K30- SLS: A Factorial study. J Appl Pharm Sci 2011; 1(09): 130-4.
[14]
Chaitanya V, Narayan PN, Kumar S, Chowdary KPR. Enhancement of solubility dissolution rate and formulation development of efavirenz tablets employing βCD and Lutrol: A Factorial study. J Glob Trends Pharm Sci 2014; 5(1): 1356-60.
[15]
Kolhe S, Chaudhari PD, More D. Dissolution and bioavailability enhancement of efavirenz by hot melt extrusion technique. J Pharm (Cairo) 2014; 4(5): 47-53.
[16]
Alves LD, de La Roca Soares MF, de Albuquerque CT, et al. Solid dispersion of efavirenz in PVP K-30 by conventional solvent and kneading methods. Carbohydr Polym 2014; 104: 166-74.
[http://dx.doi.org/10.1016/j.carbpol.2014.01.027 PMID: 24607174]
[17]
Madhavi BB, Kusum B, Chatanya ChK, Madhu MN, Harsha VS, Banji D. Dissolution enhancement of efavirenz by solid dispersion and PEGylation techniques. Int J Pharm Investig 2011; 1(1): 29-34.
[http://dx.doi.org/10.4103/2230-973X.76726 PMID: 23071917]
[18]
da Costa MA, Seiceira RC, Rodrigues CR, Hoffmeister CR, Cabral LM, Rocha HV. Efavirenz dissolution enhancement I: Co-micronization. Pharmaceutics 2012; 5(1): 1-22.
[http://dx.doi.org/10.3390/pharmaceutics5010001 PMID: 24300394]
[19]
Pawar J, Tayade A, Gangurde A, Moravkar K, Amin P. Solubility and dissolution enhancement of efavirenz hot melt extruded amorphous solid dispersions using combination of polymeric blends: A QbD approach. Eur J Pharm Sci 2016; 88: 37-49.
[http://dx.doi.org/10.1016/j.ejps.2016.04.001 PMID: 27049050]
[20]
Singh A, Majumdar S, Deng W, et al. Development and characterization of taste masked efavirenz pellets utilizing hot melt extrusion. J Drug Deliv Sci Technol 2013; 23(2): 157-63.
[http://dx.doi.org/10.1016/S1773-2247(13)50024-4]
[21]
Kotta S, Khan AW, Ansari SH, Sharma RK, Ali J. Anti HIV nanoemulsion formulation: Optimization and in vitro-in vivo evaluation. Int J Pharm 2014; 462(1-2): 129-34.
[http://dx.doi.org/10.1016/j.ijpharm.2013.12.038 PMID: 24374067]
[22]
Madhusudhan A, Reddy GB, Venkatesham M, Veerabhadram G. Design and evaluation of efavirenz loaded solid lipid nanoparticles to improve the oral bioavailability. Int J Pharm Pharm Sci 2012; 2(4): 84-9.
[23]
Gaur PK, Mishra S, Bajpai M, Mishra A. Enhanced oral bioavailability of Efavirenz by solid lipid nanoparticles: In vitro drug release and pharmacokinetics studies. BioMed Res Int 2014; 2014: 363404.
[24]
Makwana V, Jain R, Patel K, Nivsarkar M, Joshi A. Solid Lipid Nanoparticles (SLN) of Efavirenz as lymph targeting drug delivery system: Elucidation of mechanism of uptake using chylomicron flow blocking approach. Int J Pharm 2015; 495(1): 439-46.
[http://dx.doi.org/10.1016/j.ijpharm.2015.09.014 PMID: 26367780]
[25]
Gupta S, Kesarla R, Chotai N, Misra A, Omri A. systematic approach for the formulation and optimization of solid lipid nanoparticles of efavirenz by high pressure homogenization using design of experiments for brain targeting and enhanced bioavailability. BioMed Res Int 2017; 2017: 5984014.
[http://dx.doi.org/10.1155/2017/5984014 PMID: 28243600]
[26]
Pokharkar V, Patil-Gadhe A, Palla P. Efavirenz loaded nanostructured lipid carrier engineered for brain targeting through intranasal route: In-vivo pharmacokinetic and toxicity study. Biomed Pharmacother 2017; 94: 150-64.
[http://dx.doi.org/10.1016/j.biopha.2017.07.067 PMID: 28759752]
[27]
Kumar VK, Devi MA, Bhikshapathi DVRN. Development of solid self-emulsifying drug delivery systems containing efavirenz: in vitro and in vivo evaluation. Int J Pharma Bio Sci 2013; 4(1): 869-82.
[28]
Deshmukh A, Kulakrni S. Novel Self-Micro-Emulsifying Drug Delivery Systems (SMEDDS) of efavirenz. J Chem Pharm Res 2012; 4(8): 3914-9.
[29]
Selvam R, Kulkarni PK. Preparation and statistical optimization of self nanoemulsifying tablets of efavirenz using 23 factorial designs. Int J Drug Deliv 2014; 6: 50-7.
[30]
Reddy MS, Reddy NS, Reddy SM. Solubility enhancement of poorly water soluble drug efavirenz by solid self-emulsifying drug delivery systems. Int J Pharma Res Rev 2014; 3(4): 20-8.
[31]
Jenita JL, Chocalingam V, Wilson B. Albumin nanoparticles coated with polysorbate 80 as a novel drug carrier for the delivery of antiretroviral drug-Efavirenz. Int J Pharm Investig 2014; 4(3): 142-8.
[http://dx.doi.org/10.4103/2230-973X.138348 PMID: 25126528]
[32]
Tshweu L, Katata L, Kalombo L, et al. Enhanced oral bioavailability of the antiretroviral efavirenz encapsulated in poly(epsilon-caprolactone) nanoparticles by a spray-drying method. Nanomedicine (Lond) 2014; 9(12): 1821-33.
[http://dx.doi.org/10.2217/nnm.13.167 PMID: 24364871]
[33]
Jain S, Sharma JM, Agrawal AK, Mahajan RR. Surface stabilized efavirenz nanoparticles for oral bioavailability enhancement. J Biomed Nanotechnol 2013; 9(11): 1862-74.
[http://dx.doi.org/10.1166/jbn.2013.1683 PMID: 24059085]
[34]
Hari BNV, Narayanan N, Dhevedaran K. Efavirenz–eudragit E-100 nanoparticle-loaded aerosol foam for sustained release: In-vitro and ex-vivo evaluation. Chem Pap 2015; 69(2): 358-67.
[35]
Date AA, Shibata A, Goede M, et al. Development and evaluation of a thermosensitive vaginal gel containing raltegravir+efavirenz loaded nanoparticles for HIV prophylaxis. Antiviral Res 2012; 96(3): 430-6.
[http://dx.doi.org/10.1016/j.antiviral.2012.09.015 PMID: 23041201]
[36]
Chiappetta DA, Hocht C, Taira C, Sosnik A. Efavirenz-loaded polymeric micelles for pediatric anti-HIV pharmacotherapy with significantly higher oral bioavailability. [corrected]. Nanomedicine (Lond) 2010; 5(1): 11-23.
[http://dx.doi.org/10.2217/nnm.09.90 PMID: 20025460]
[37]
Destache CJ, Belgum T, Christensen K, Shibata A, Sharma A, Dash A. Combination antiretroviral drugs in PLGA nanoparticle for HIV-1. BMC Infect Dis 2009; 9: 198.
[http://dx.doi.org/10.1186/1471-2334-9-198 PMID: 20003214]
[38]
Katata L, Tshweu L, Naidoo S, Kalombo L, Swai H. Design and formulation of nano-sized spray dried efavirenz-part I: Influence of formulation parameters. J Nanopart Res 2012; 14: 1-8.
[http://dx.doi.org/10.1007/s11051-012-1247-0]
[39]
Dutta T, Agashe HB, Garg M, Balakrishnan P, Kabra M, Jain NK. Poly (propyleneimine) dendrimer based nanocontainers for targeting of efavirenz to human monocytes/macrophages in vitro. J Drug Target 2007; 15(1): 89-98.
[http://dx.doi.org/10.1080/10611860600965914 PMID: 17365278]
[40]
Dutta T, Garg M, Jain NK. Targeting of efavirenz loaded tuftsin conjugated poly(propyleneimine) dendrimers to HIV infected macrophages in vitro. Eur J Pharm Sci 2008; 34(2-3): 181-9.
[http://dx.doi.org/10.1016/j.ejps.2008.04.002 PMID: 18501568]
[41]
P V Choudhary RK Narne R. Efavirenz loaded novel citric acid dendritic architecture for increased solubility and sustained delivery. J Pharm Drug Deliv Res 2012; 1: 1-5.
[42]
Seremeta KP, Chiappetta DA, Sosnik A. Poly(ε-caprolactone), Eudragit® RS 100 and poly(ε-caprolactone)/Eudragit® RS 100 blend submicron particles for the sustained release of the antiretroviral efavirenz. Colloids Surf B Biointerfaces 2013; 102: 441-9.
[http://dx.doi.org/10.1016/j.colsurfb.2012.06.038 PMID: 23010128]
[43]
Liptrott NJ, Giardiello M, McDonald TO, Rannard SP, Owen A. Assessment of interactions of efavirenz solid drug nanoparticles with human immunological and haematological systems. J Nanobiotechnology 2018; 16(1): 22.
[http://dx.doi.org/10.1186/s12951-018-0349-y PMID: 29544545]
[44]
Roy U, Drozd V, Durygin A, et al. Characterization of Nanodiamond- based anti-HIV drug Delivery to the Brain. Sci Rep 2018; 8(1): 1603.
[http://dx.doi.org/10.1038/s41598-017-16703-9 PMID: 29371638]
[45]
Curley P, Rajoli RK, Moss DM, et al. Efavirenz is predicted to accumulate in brain tissue: An in silico, in vitro, and in vivo investigation. Antimicrob Agents Chemother 2016; 61(1): 1-12.
[PMID: 27799216]
[46]
Nightingale S, Chau TT, Fisher M, et al. Efavirenz and metabolites in cerebrospinal fluid: Relationship with CYP2B6 c.516G→T genotype and perturbed blood-brain barrier due to Tuberculous Meningitis. Antimicrob Agents Chemother 2016; 60(8): 4511-8.
[http://dx.doi.org/10.1128/AAC.00280-16 PMID: 27161633]
[47]
Rao KS, Ghorpade A, Labhasetwar V. Targeting anti-HIV drugs to the CNS. Expert Opin Drug Deliv 2009; 6(8): 771-84.
[http://dx.doi.org/10.1517/17425240903081705 PMID: 19566446]
[48]
Wang Y, Li P, Truong-Dinh Tran T, Zhang J, Kong L. Manufacturing techniques and surface engineering of polymer based nanoparticles for targeted drug delivery to cancer. Nanomaterials (Basel) 2016; 6(2): 1-18.
[http://dx.doi.org/10.3390/nano6020026 PMID: 28344283]
[49]
Wang Y, Li P, Peng Z, She FH, Kong LX. Microencapsulation of nanoparticles with enhanced drug loading for pH-sensitive oral drug delivery for the treatment of colon cancer. J Appl Ploym Sci 2013; pp. 714-20.
[50]
Wang Y, Li P, Kong L. Chitosan-modified PLGA nanoparticles with versatile surface for improved drug delivery. AAPS PharmSciTech 2013; 14(2): 585-92.
[http://dx.doi.org/10.1208/s12249-013-9943-3 PMID: 23463262]
[51]
Li P, Yang Z, Wang Y, et al. Microencapsulation of coupled folate and chitosan nanoparticles for targeted delivery of combination drugs to colon. J Microencapsul 2015; 32(1): 40-5.
[http://dx.doi.org/10.3109/02652048.2014.944947 PMID: 25198909]
[52]
Wang Y, Li P, Chen L, Gao W, Zeng F, Kong LX. Targeted delivery of 5-fluorouracil to HT-29 cells using high efficient folic acid-conjugated nanoparticles. Drug Deliv 2015; 22(2): 191-8.
[http://dx.doi.org/10.3109/10717544.2013.875603 PMID: 24437926]
[53]
Vaghari H, Jafarizadeh-Malmiri H, Mohammadlou M, et al. Application of magnetic nanoparticles in smart enzyme immobilization. Biotechnol Lett 2016; 38(2): 223-33.
[http://dx.doi.org/10.1007/s10529-015-1977-z PMID: 26472272]
[54]
Ansari SA, Husain Q. Potential applications of enzymes immobilized on/in nano materials: A review. Biotechnol Adv 2012; 30(3): 512-23.
[http://dx.doi.org/10.1016/j.biotechadv.2011.09.005] [PMID: 21963605]
[55]
Husain Q. Nanomaterials as novel supports for the immobilization of amylolytic enzymes and their applications: A review. Biocatalysis 2017; 3(1): 37-53.
[http://dx.doi.org/10.1515/boca-2017-0004]
[56]
Wang Y, Zhang S, Haque E, et al. Immobilisation of microperoxidase- 11 into layered MoO3 for applications of enzymatic conversion. Appl Mater Today 2019; 16: 185-92.
[http://dx.doi.org/10.1016/j.apmt.2019.05.008]
[57]
Kumar P, Lakshmi YS, Kondapi AK. An oral formulation of efavirenz-loaded lactoferrin nanoparticles with improved biodistribution and pharmacokinetic profile. HIV Med 2017; 18(7): 452-62.
[http://dx.doi.org/10.1111/hiv.12475 PMID: 28000390]
[58]
Belgamwar A, Khan S, Yeole P. Intranasal chitosan-g-HPβCD nanoparticles of efavirenz for the CNS targeting. Artif Cells Nanomed Biotechnol 2018; 46(2): 374-86.
[http://dx.doi.org/10.1080/21691401.2017.1313266] [PMID: 28423949]
[59]
Nunes R, Araújo F, Barreiros L, et al. Non-covalent PEG coating of nanoparticle drug carriers improves the local pharmacokinetics of rectal anti-HIV microbicides. ACS Appl Mater Interfaces 2018; 10(41): 34942-53.
[http://dx.doi.org/10.1021/acsami.8b12214 PMID: 30234288]
[60]
Reddy BP, Khadgapathi P, Reddy GK. bioequivalent formulation of efavirenz. us patent 9138412b2, 2009.
[61]
Higgins UBJ, Thompson CK, Katdare AV. efavirenz compressed tablet formulation. wo patent 1999061026a1, 1998.
[62]
Makooi-Morehead WT, Buehler JD, Landmann BR. formulation of fast-dissolving efavirenz capsules or tablets using superdisintegrants. us patent 6238695b1 1998.
[63]
Giardiello MN, McDonald TO, Owen A, Rannard SP, Martin PJ, Smith DL. compositions of efavirenz. us patent 9498438b2, 2011.
[64]
Roy U, Ding H, Nair M. materials and methods for targeting therapeutic compositions to gut-associated lymphoid tissue (galt). us patent 15437878 2017.
[65]
Malhotra G, Purandare SM. pharmaceutical compositions comprising efavirenz. wo patent 2015059466a1, 2015.
[66]
Destache CJ. Nanoparticles and methods of use. us patent 8846096b2, 2014.

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