Login Register Cart 0
Generic placeholder image

Current HIV Research

Editor-in-Chief

ISSN (Print): 1570-162X
ISSN (Online): 1873-4251

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Evaluation of the Properties of Encapsulated Stavudine Microparticulate Lipid-based Drug Delivery System in Immunocompromised Wistar Rats

Author(s): Salome A. Chime*, Godswill C. Onunkwo and Anthony A. Attama

Volume 18, Issue 4, 2020

Page: [237 - 247] Pages: 11

DOI: 10.2174/1570162X18666200510010738

Price: $65

Abstract

Background: Lipid-based formulations have been confirmed to lower some side effects of drugs and can be tailor-made to offer sustained drug release of drugs with short half-life like stavudine.

Aim: This study aimed to evaluate the immunomodulatory properties of stavudine-loaded solid lipid microparticles (SLMs) using immunocompromised Wistar rats.

Methods: The SLMs were formulated by the homogenization method. The optimized batches were used for further in vivo studies. The effect of formulation on the CD4 count and the haematological properties of immunocompromised Wistar rats were studied.

Results: The particle size range was 4 -8 μm, EE range was 85-93 % and maximum drug release was observed at 10 h. The CD4 cells increased from 115 ± 3.17 cell/mm3 at day zero to 495 ± 5.64 cell/mm3 at day 14 of treatment and 538 ± 6.31 cell/mm3 at day 21. The red blood cells increased from 2.64 ± 1.58 (x 106/mm3) at day zero to 6.96 ± 3.47 (x 106/mm3) at day 14 and 7.85 ± 3.64 (x 106/mm3) at day 21. PCV increased significantly (p < 0.05) to about 42-50 % at day 21 in the groups that received the SLMs formulations. White blood cells (WBC) also were 12 x 103/mm3, for SLM formulations, while the rats that received plain stavudine exhibited WBC of 9.6 x 103/mm3 at day 21. The histopathological studies revealed that oral stavudine-loaded SLMs had no significant damage to the kidney, liver, spleen and the brain of Wistar rats.

Conclusion: The formulations exhibited significantly higher immunomodulatory properties than plain stavudine (p<0.05) and showed good properties for once daily oral administration and could be a better alternative to plain stavudine tablets for the management of patients living with HIV.

Keywords: CD4 cells, histopathology, lymphocytes, neutrophils, RBC, stavudine, solid lipid microparticles, white blood cells.

« Previous Next »
Graphical Abstract

[1]
Sweetman SC. In; Martindale; The complete reference. 33rd ed. London: Pharmaceutical Press 2002; p. 641.
[2]
Singh KK. Conversion of stavudine lipid nanoparticles into dry powder. Int J Pharma Bio Sci 2011; 2(1): 443-57.
[3]
Hardman JG, Limbird LE, Molinoff PB, Ruddeon RW. In Gilman In Goodman and Gilman’s the Pharmacological Basis of Therapeutics. New York: McGraw–Hill 2001; Vol. X: p. 1357.
[4]
Zhou J, Paton NI, Ditangco R, et al. Experience with the use of a first-line regimen of stavudine, lamivudine and nevirapine in patients in the TREAT Asia HIV Observational Database. HIV Med 2007; 8(1): 8-16.
[http://dx.doi.org/10.1111/j.1468-1293.2007.00417.x] [PMID: 17305926]
[5]
Ranjit KP, Suresh VK, Vinod R, Sandeep HN, Someshwara RB, Ashok KP. Design and characterization of controlled release matrix tablets of stavudine. Int J Pharm Clin Res 2010; 2(1): 46-50.
[6]
Sawant VA, Unhale RB, Shende VS, Borkar SN, Chatap VK. Formulation in vitro release kinetic study of stavudine from sustained release matrix tablet containing hydrophilic and hydrophobic polymers. Indian J Nov Drug Deliv 2009; 1(1): 36-41.
[7]
Dunge A, Chakraborti AK, Singh S. Mechanistic explanation to the variable degradation behaviour of stavudine and zidovudine under hydrolytic, oxidative and photolytic conditions. J Pharm Biomed Anal 2004; 35(4): 965-70.
[http://dx.doi.org/10.1016/j.jpba.2004.03.007] [PMID: 15193743]
[8]
Dhirendra K, Vivek D, Shaila L, Brajesh P, Kavita RG, Sarvesh P. Design and evaluation of sustained-release matrix once daily formulation of stavudine. Int J Drug Deliv 2010; 2: 125-34.
[http://dx.doi.org/10.5138/ijdd.2010.0975.0215.02021]
[9]
UNAIDS Global HIV & AIDS statistics — 2019 fact sheet. Available at; https://www.unaids.org/en/resources/fact-sheet[Accessed 11th September, 2019]..
[10]
Stuchlík M, Zák S. Lipid-based vehicle for oral drug delivery. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2001; 145(2): 17-26.
[http://dx.doi.org/10.5507/bp.2001.008] [PMID: 12426768]
[11]
Li W. Lipid formulation: successful stories and prospective future. Trends Bio Pharma Ind 2006; 3: 31-5.
[12]
Humberstone AJ, Charman WN. Lipid-based vehicles for the oral delivery of poorly water-soluble drugs. Adv Drug Deliv Rev 1997; 25: 103-28.
[http://dx.doi.org/10.1016/S0169-409X(96)00494-2]
[13]
Gonnade YR, Niranjane K, Arati A. Lipid: an emerging platform for lipid based drug delivery system. World J Pharm Pharmaceut 2014; 3(4): 572-89.
[14]
Foubert I. In The lipid handbook.3rd ed Gunstone FD, Harwood JL, Dijkstra AJ (eds). CRC Press, Boca Raton 2007 In:
[15]
Shrestha H, Bala R, Arora S. Lipid-based drug delivery systems. J Pharm (Cairo) 2014; 2014801820
[http://dx.doi.org/10.1155/2014/801820] [PMID: 26556202]
[16]
Cerpnjak K, Zvonar A, Gašperlin M, Vrečer F. Lipid-based systems as a promising approach for enhancing the bioavailability of poorly water-soluble drugs. Acta Pharm 2013; 63(4): 427-45.
[http://dx.doi.org/10.2478/acph-2013-0040] [PMID: 24451070]
[17]
Dahan A, Hoffman A. 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 2008; 129(1): 1-10.
[http://dx.doi.org/10.1016/j.jconrel.2008.03.021] [PMID: 18499294]
[18]
Attama AA, Schicke BC, Müller-Goymann CC. Further characterization of theobroma oil-beeswax admixtures as lipid matrices for improved drug delivery systems. Eur J Pharm Biopharm 2006; 64(3): 294-306.
[http://dx.doi.org/10.1016/j.ejpb.2006.06.010] [PMID: 16949805]
[19]
Nanjwade BK, Patel DJ, Udhani RA, Manvi FV. Functions of lipids for enhancement of oral bioavailability of poorly water-soluble drugs. Sci Pharm 2011; 79(4): 705-27.
[http://dx.doi.org/10.3797/scipharm.1105-09] [PMID: 22145101]
[20]
Hauss DJ. Lipid-based systems for oral drug delivery: Enhancing the bioavailability of poorly water-soluble drugs. Am Pharm Rev 2002; 5: 22-8.
[21]
Garg BJ, Garg NK, Beg S, Singh B, Katare OP. Nanosized ethosomes-based hydrogel formulations of methoxsalen for enhanced topical delivery against vitiligo: formulation optimization, in vitro evaluation and preclinical assessment J Drug Target 2016; 24(3): 233-46.
[http://dx.doi.org/10.3109/1061186X.2015.1070855] [PMID: 26267289]
[22]
Junyaprasert VB, Boonme P, Songkro S, Krauel K, Rades T. Transdermal delivery of hydrophobic and hydrophilic local anesthetics from o/w and w/o Brij 97-based microemulsions. J Pharm Pharm Sci 2007; 10(3): 288-98.
[PMID: 17727792]
[23]
Junyaprasert VB, Boonme P, Wurster DE, Rades T. Aerosol OT microemulsions as carriers for transdermal delivery of hydrophobic and hydrophilic local anesthetics. Drug Deliv 2008; 15(5): 323-30.
[http://dx.doi.org/10.1080/10717540802035319] [PMID: 18763163]
[24]
Junyaprasert VB, Boonsaner P, Leatwimonlak S, Boonme P. Enhancement of the skin permeation of clindamycin phosphate by Aerosol OT/1-butanol microemulsions. Drug Dev Ind Pharm 2007; 33(8): 874-80.
[http://dx.doi.org/10.1080/03639040600975097] [PMID: 17729105]
[25]
Nagaich U, Gulati N. Nanostructured lipid carriers (NLC) based controlled release topical gel of clobetasol propionate: design and in vivo characterization. Drug Deliv Transl Res 2016; 6(3): 289-98.
[http://dx.doi.org/10.1007/s13346-016-0291-1] [PMID: 27072979]
[26]
Ragwa MF, Noha SE, Amal HE, Safaa SE. Lipid-based nanocarriers for ocular drug deliveryNanostructures for Drug Delivery Micro Nano Tech. Elsevier 2017; pp. 495-522.
[27]
Khan A, Aqil M, Imam SS, et al. Temozolomide loaded nano lipid based chitosan hydrogel for nose to brain delivery: Characterization, nasal absorption, histopathology and cell line study. Int J Biol Macromol 2018; 116: 1260-7.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.05.079] [PMID: 29775717]
[28]
Dilip KP, Surendra T, Suresh KN, Roohi K. Nanostructured lipid carrier (NLC) a modern approach for topical delivery: a review. World J Pharm Pharm Sci 2003; 2(3): 921-38.
[29]
Moazeni M, Kelidari HR, Saeedi M, et al. Time to overcome fluconazole resistant Candida isolates: Solid lipid nanoparticles as a novel antifungal drug delivery system. Colloids Surf B Biointerfaces 2016; 142: 400-7.
[http://dx.doi.org/10.1016/j.colsurfb.2016.03.013] [PMID: 26974361]
[30]
Das S, Chaudhury A. Recent advances in lipid nanoparticle formulations with solid matrix for oral drug delivery. AAPS PharmSciTech 2011; 12(1): 62-76.
[http://dx.doi.org/10.1208/s12249-010-9563-0] [PMID: 21174180]
[31]
Kumar D, Sharma D, Singh G, Singh M, Rathore MS. Lipoidal soft hybrid biocarriers of supramolecular construction for drug delivery. Int Sch Res Not 2012; 2012: 1-14.
[http://dx.doi.org/10.5402/2012/474830]]
[32]
Domb AJ, Maniar M. Liposphere for controlled delivery of substances. Eurpean Patent 1996.EP0502119.
[33]
Domb AJ, Bergelson L, Amselem S. Lipospheres for controlled delivery of substances. In: Benita S (ed), microencapsulation: method and industrial applications. Marcel Dekker Inc. NY. 1996; pp. 337-410.
[34]
Attama AA, Nkemnele MO. In vitro evaluation of drug release from self micro-emulsifying drug delivery systems using a biodegradable homolipid from Capra hircus. Int J Pharm 2005; 304(1-2): 4-10.
[http://dx.doi.org/10.1016/j.ijpharm.2005.08.018] [PMID: 16198521]
[35]
Gugu TH, Chime SA, Attama AA. Solid lipid microparticles: An approach for improving oral bioavailability of aspirin. As. J Pharm Sci 2015; 10(5): 425-32.
[36]
Nnamani PO, Ogbonna CC, Dibua EU, Ezedigboh NN, Attama AA. Sustained circulation time of glibenclamide from pegylated solid lipid microparticles. Int J Novel Drug Deliv Tech 2012; 2(2): 283-90.
[37]
Umeyor EC, Kenechukwu FC, Ogbonna JD, Chime SA, Attama A. Preparation of novel solid lipid microparticles loaded with gentamicin and its evaluation in vitro and in vivo. J Microencapsul 2012; 29(3): 296-307.
[http://dx.doi.org/10.3109/02652048.2011.651495] [PMID: 22283701]
[38]
Momoh MA, Akpa PA, Attama AA. Phospholipon 90G based SLMs loaded with ibuprofen: an oral antiinflammatory and gastrointestinal sparing evaluation in rats. Pak J Zool 2012; 44(6): 1657-64.
[39]
Li RJ, Ying X, Zhang Y, et al. All-trans retinoic acid stealth liposomes prevent the relapse of breast cancer arising from the cancer stem cells. J Control Release 2011; 149(3): 281-91.
[http://dx.doi.org/10.1016/j.jconrel.2010.10.019] [PMID: 20971141]
[40]
Li X, Ding L, Xu Y, Wang Y, Ping Q. Targeted delivery of doxorubicin using stealth liposomes modified with transferrin. Int J Pharm 2009; 373(1-2): 116-23.
[http://dx.doi.org/10.1016/j.ijpharm.2009.01.023] [PMID: 19429296]
[41]
Umeyor CE, Kenechukwu FC, Uronnachi EM, Osonwa UE, Nwakile CD. Solid lipid microparticles (SLMs): An effective lipid based technology for controlled drug delivery. Am J Pharm Tech Res 2012; 2(6): 1-18.
[42]
Luigi B, Elena U. Lipid Nano- and microparticles: An overview of patent-related research. J Nanomat 2019; pp. 1-22.
[43]
EL- Kamel HA. AL-Fagih MI, Alsarra AI. Testosterone solid lipid micro particles for transdermal drug delivery formulation and physicochemical characterization. J Microencapsul 2007; 24(5): 457-75.
[http://dx.doi.org/10.1080/02652040701368865] [PMID: 17578735]
[44]
Sato K. Crystallization behavior of fats and lipids: a review. Chem Eng Sci 2001; 56: 2255-65.
[http://dx.doi.org/10.1016/S0009-2509(00)00458-9]
[45]
Garti N. In Physical properties of lipids.Marangoni AG, Narine SS (eds)Boca Raton: CRC Press 2002.
[46]
Pouton CW. Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. Eur J Pharm Sci 2006; 29(3-4): 278-87.
[http://dx.doi.org/10.1016/j.ejps.2006.04.016] [PMID: 16815001]
[47]
Pouton CW, Porter CJ. Formulation of lipid-based delivery systems for oral administration: materials, methods and strategies. Adv Drug Deliv Rev 2008; 60(6): 625-37.
[http://dx.doi.org/10.1016/j.addr.2007.10.010] [PMID: 18068260]
[48]
Porter CJH, Charman WN. Uptake of drugs into intestinal lymphatics after oral administration. Adv Drug Deliv Rev 1997; 25: 71-90.
[http://dx.doi.org/10.1016/S0169-409X(96)00492-9]
[49]
Porter CJ, Trevaskis NL, Charman WN. Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nat Rev Drug Discov 2007; 6(3): 231-48.
[http://dx.doi.org/10.1038/nrd2197] [PMID: 17330072]
[50]
Rangel-Yagui CO, Pessoa A Jr, Tavares LC. Micellar solubilization of drugs. J Pharm Pharm Sci 2005; 8(2): 147-65.
[PMID: 16124926]
[51]
Sagalowicz L, Mezzenga R, Leser ME. Investigating reversed liquid crystalline mesophases. Cur Opn Col Int Sci 2006; 11(4): 224-9.
[http://dx.doi.org/10.1016/j.cocis.2006.07.002]
[52]
Clogston J, Caffrey M. Controlling release from the lipidic cubic phase. Amino acids, peptides, proteins and nucleic acids. J Control Release 2005; 107(1): 97-111.
[http://dx.doi.org/10.1016/j.jconrel.2005.05.015] [PMID: 15990192]
[53]
Chime SA, Attama AA, Builders PF, Onunkwo GC. Sustained-release diclofenac potassium-loaded solid lipid microparticle based on solidified reverse micellar solution: in vitro and in vivo evaluation. J Microencapsul 2013; 30(4): 335-45.
[http://dx.doi.org/10.3109/02652048.2012.726284] [PMID: 23057661]
[54]
Kenechukwu FC, Attama AA, Emmanuel CI, et al. Novel intravaginal drug delivery system based on molecularly pegylated lipid matrices for improved antifungal activity of miconazole nitrate. Biomed Res 2018; 200183714329
[55]
Fouad EA, El-badry M, Mahrous GM, Alsarra V, Alashbban Z, Alanazi FK. In vitro investigation for embedding dextromethorphan in lipids using spray drying. Digest J Nano Bio 2011; 6(3): 1129-39.
[56]
Kuentz M. Lipid-based formulations for oral delivery of lipophilic drugs Drug Discov. Today Technol 2012.
[57]
Chime SA, Onyishi IV. Lipid-based drug delivery systems (LDDS): Recent advances and applications of lipids in drug delivery. Afr J Pharm Pharmacol 2013; 7(48): 3034-59.
[http://dx.doi.org/10.5897/AJPPX2013.0004]
[58]
Uronnachi EM, Ogbonna JDN, Kenechukwu FC, et al. Pharmacokinetics and biodistribution of zidovudine loaded in a solidified reverse micellar delivery system. Int J Drug Deliv 2013; 5: 73-80.
[59]
Heroor S, Beknal A, Mahurkar N. Immunomodulatory activity of methanolic extracts of Ficus glomerata roxb. leaf, fruit and bark in cyclophosphamide induced mice. Int J Modern Bot 2011; 1(1): 4-7.
[http://dx.doi.org/10.5923/j.ijmb.20110101.02]
[60]
Ohwada K. Improvement of cardiac puncture in mice. Jikken Dobutsu 1986; 35(3): 353-5.
[http://dx.doi.org/10.1538/expanim1978.35.3_353] [PMID: 3770089]
[61]
Ofem O, Ani E, Eno A. Effect of aqueous leaves extract of Ocimum gratissimum on hematological parameters in rats. Int J Appl Basic Med Res 2012; 2(1): 38-42.
[http://dx.doi.org/10.4103/2229-516X.96807] [PMID: 23776807]
[62]
Bancroft JD, Stevens A. Theory and Practice of Histological Techniques. Edinburgh: Churchill Livingstone 1977; pp. 16-64.
[63]
Brown SA, Chime SA, Attama AA, Agu C, Onunkwo GC. In vitro and in vivo characterisation of piroxicam-loaded dika wax lipospheres. Trop J Pharm Res 2013; 12(1): 33-8.
[http://dx.doi.org/10.4314/tjpr.v12i1.6]
[64]
Obitte NC, Ofokansi KC, Chime SA, Odimegwu DC, Ezema AO, Odoh UE. A preliminary attempt to address indomethacin’s poor water solubility using solid self-emulsifying drug delivery system as a carrier. Afr J Pharm Pharmacol 2013; 7(46): 2918-27.
[http://dx.doi.org/10.5897/AJPP2012.1510]
[65]
Khopade AJ, Jain NK. Long-circulating lipospheres targeted to the inflammed tissue. Pharmazie 1997; 52(2): 165-6.
[PMID: 9122278]
[66]
Eradel MS, Gungor S, Ozsoy Y, Araman A. Preparation and in vitro evaluation of indomethacin loaded solid lipid microparticles. Acta Pharmaceiutical Sciencia 2009; 51: 203-10.
[67]
Obitte NC, Chime SA, Magaret AA, Attama AA, Onyishi IV, Brown SA. Some in vitro and pharmacodynamic evaluation of indomethacin solid lipid microparticles. Afr J Pharm Pharmacol 2012; 6(30): 2309-17.
[http://dx.doi.org/10.5897/AJPP12.524]
[68]
Long C, Zhang L, Qian Y. Preparation and crystal modification of Ibuprofen-loaded solid lipid microparticles. Chin J Chem Eng 2006; 14(4): 518-25.
[http://dx.doi.org/10.1016/S1004-9541(06)60107-9]
[69]
Attama AA, Okafor CE, Builders PF, Okorie O. Formulation and in vitro evaluation of a PEGylated microscopic lipospheres delivery system for ceftriaxone sodium. Drug Deliv 2009; 16(8): 448-57.
[http://dx.doi.org/10.3109/10717540903334959] [PMID: 19839789]
[70]
Rat hematology https://en.wikivet.net/Rat_Haematology Assessed 19th March. 2020.
[71]
Archer RK, Festing MFW, Riley J. Haematology of conventionally-maintained Lac:P outbred Wistar rats during the 1st year of life. Lab Anim 1982; 16(2): 198-200.
[http://dx.doi.org/10.1258/002367782781110223] [PMID: 7078067]
[72]
Kampfmann I, Bauer N, Johannes S, Moritz A. Differences in hematologic variables in rats of the same strain but different origin. Vet Clin Pathol 2012; 41(2): 228-34.
[http://dx.doi.org/10.1111/j.1939-165X.2012.00427.x] [PMID: 22551195]
[73]
Creskoff AJ, Fitz-Hugh T, Farris EJ. Hematology of the rat The rat in laboratory investigation. 2nd ed. Philadelphia: Lippincott 1949; pp. 406-20.
[74]
Archer RK, Riley J. Standardized method for bleeding rats. Lab Anim 1981; 15(1): 25-8.
[http://dx.doi.org/10.1258/002367781780958586] [PMID: 7265892]
[75]
Didisheim P, Hattori K, Lewis JH. Hematologic and coagulation studies in various animal species. J Lab Clin Med 1959; 53(6): 866-75.
[PMID: 13665129]
[76]
Burns KF, De Lannoy CW Jr. Compendium of normal blood values of laboratory animals with indication of variations. I. Random-sexed populations of small animals. Toxicol Appl Pharmacol 1966; 8(3): 429-37.
[http://dx.doi.org/10.1016/0041-008X(66)90052-4] [PMID: 5962996]

Rights & Permissions Print Cite
Article Metrics
29
Wayfinder Image
World AIDS Day
© 2024 Bentham Science Publishers | Privacy Policy