This work aimed to develop and assess terpene encapsulated polycaprolactone (PCL) nanoparticles for topical delivery of hydrocortisone (HC). Formulations were designed to investigate the effect of terpene/PCL ratio and concentration of surfactant on physicochemical characteristics. Structural analyses were studied using differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy techniques. Ex vivo skin permeation and anti-inflammatory activity of HC were also appraised. Results showed that the physicochemical characteristics were particularly influenced by terpene/PCL ratio and concentration of surfactant. The selected formulation (F6) showed core-shell structure and good encapsulation of HC in less crystalline state. Higher skin flux (366.11 ± 32.8 µg/cm2/h) and permeability coefficient (17.57 ± 2.6 × 102 cm/h) of HC from gel based on F6 were observed when compared with crude drug gel. Anti-inflammatory activity of HC was significantly improved and showed sustained therapeutic action when using gel based on F6. Collectively, these findings suggest that terpene encapsulated PCL nanoparticles can potentially deliver HC through the skin.
FazliY, ShariatiniaZ, KohsariI, et al.A novel chitosan-polyethylene oxide nanofibrous mat designed for controlled co-release of hydrocortisone and imipenem/cilastatin drugs. Int J Pharm, 2016; 513(1–2):636–647.
2.
FiniA, BergamanteV, CeschelGC, et al.Control of transdermal permeation of hydrocortisone acetate from hydrophilic and lipophilic formulations. AAPS PharmSciTech, 2008; 9(3):762–768.
3.
DavisAF, GyurikRJ, HadgraftJ, et al.Formulation strategies for modulating skin permeation. In: Dermatological and transdermal formulations. CRC Press; 2002. pp. 289–336.
4.
DevosSA, Van Der ValkPGM. Relevance and reproducibility of patch‐test reactions to corticosteroids. Contact Dermatitis, 2001; 44(6):362–365.
5.
HuangX, TanojoH, LennJ, et al.A novel foam vehicle for delivery of topical corticosteroids. J Am Acad Dermatol, 2005; 53(1 Suppl 1):S26–S38.
6.
PanconesiE, LottiT. Steroids versus nonsteroids in the treatment of cutaneous inflammation: Therapeutic modalities for office use. Arch Dermatol Res, 1992; 284(Suppl 1):S37–S41.
7.
OrientiI, ZecchiV, CeschelG, et al.Controlled release of hydrocortisone acetate from dermal bases. Eur J Drug Metab Pharmacokinet, 1991;Spec No 3:466–472.
8.
RefaiH, MuCC. The influence of dilution of topical semisolid preparations on hydrocortisone permeation through excised human stratum corneum. Eur J Pharm Biopharm, 2002; 54(2):143–150.
9.
ArkwrightPD, MotalaC, SubramanianH, et al.; Atopic Dermatitis Working Group of the Allergic Skin Diseases Committee of the AAAAI. Management of difficult-to-treat atopic dermatitis. J Allergy Clin Immunol Pract, 2013; 1(2):142–151.
10.
AbboudD, HansonJ. Chemokine neutralization as an innovative therapeutic strategy for atopic dermatitis. Drug Discov Today, 2017; 22(4):702–711.
11.
KassemMA, RahmanAAA, GhorabMM, et al.Nanosuspension as an ophthalmic delivery system for certain glucocorticoid drugs. Int J Pharm, 2007; 340(1–2):126–133.
12.
RiviereJE, BrooksJD. Predicting skin permeability from complex chemical mixtures: Dependency of quantitative structure permeation relationships on biology of skin model used. Toxicol Sci, 2011; 119(1):224–232.
13.
TanQ, LiuW, GuoC, et al.Preparation and evaluation of quercetin-loaded lecithin-chitosan nanoparticles for topical delivery. Int J Nanomedicine, 2011; 6:1621–1630.
14.
KesisoglouF, PanmaiS, WuY. Nanosizing—oral formulation development and biopharmaceutical evaluation. Adv Drug Deliv Rev, 2007; 59(7):631–644.
15.
RosadoC, SilvaC, ReisCP. Hydrocortisone-loaded poly (ε-caprolactone) nanoparticles for atopic dermatitis treatment. Pharm Dev Technol, 2013; 18(3):710–718.
16.
ShorL. Novel fabrication development for the application of polycaprolactone and composite polycaprolactone/hydroxyapitite scaffolds for bone tissue engineering. Vol. 70. 2008.
17.
KumariA, YadavSK, YadavSC. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B Biointerfaces, 2010; 75(1):1–18.
18.
SinhaVR, BansalK, KaushikR, et al.Poly-ϵ-caprolactone microspheres and nanospheres: An overview. Int J Pharm, 2004; 278(1):1–23.
19.
BhavsarMD, AmijiMM. Development of novel biodegradable polymeric nanoparticles-in-microsphere formulation for local plasmid DNA delivery in the gastrointestinal tract. AAPS PharmSciTech, 2008; 9(1):288–294.
20.
Alvarez-RomanR, NaikA, KaliaYN, et al.Enhancement of topical delivery from biodegradable nanoparticles. Pharm Res, 2004; 21:1818–1825.
21.
SinglaV, SainiS, SinghG. Penetration enhancers: A novel strategy for enhancing transdermal drug delivery. Int Res J Pharm, 2011; 2(12):20–24.
22.
DragicevicN, MaibachHI. Percutaneous penetration enhancers drug penetration into/through the skin: Methodology and general considerations. Percutaneous Penetration Enhanc Drug Penetration Into/Through Ski Methodol Gen Considerations. 2017; 1–414.
23.
El-KattanAF, AsbillCS, MichniakBB. The effect of terpene enhancer lipophilicity on the percutaneous permeation of hydrocortisone formulated in HPMC gel systems. Int J Pharm, 2000; 198(2):179–189.
CuiY, LiL, ZhangL, et al.Enhancement and mechanism of transdermal absorption of terpene-induced propranolol hydrochloride. Arch Pharm Res, 2011; 34(9):1477–1485.
26.
YiQ-F, YanJ, TangS-Y, et al.Effect of borneol on the transdermal permeation of drugs with differing lipophilicity and molecular organization of stratum corneum lipids. Drug Dev Ind Pharm, 2016; 42(7):1086–1093.
27.
SakeenaMHF, ElrashidSM, MuthannaFA, et al.Effect of limonene on permeation enhancement of ketoprofen in palm oil esters nanoemulsion. J Oleo Sci, 2010; 59(7):395–400.
28.
Dragicevic-CuricN, GräfeS, AlbrechtV, et al.Topical application of temoporfin-loaded invasomes for photodynamic therapy of subcutaneously implanted tumours in mice: A pilot study. J Photochem Photobiol B, 2008; 91(1):41–50.
29.
FrajA, JaâfarF, MartiM, et al.A comparative study of oregano (Origanum vulgare L.) essential oil-based polycaprolactone nanocapsules/microspheres : Preparation, physicochemical characterization, and storage stability. Ind Crop Prod, 2019; 140:111669.
30.
FessiH, PuisieuxF, DevissaguetJP, et al.Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int J Pharm, 1989; 55(1):R1–R4.
31.
AlsaidanOA, ElmowafyM, ShalabyK, et al.Hydrocortisone-loaded lipid—Polymer hybrid nanoparticles for controlled topical delivery : Formulation design optimization and in vitro and in vivo appraisal. ACS Omega, 2023; 8(21):18714–18725.
32.
ZhaoL, WangY, ZhaiY, et al.Ropivacaine loaded microemulsion and microemulsion-based gel for transdermal delivery: Preparation, optimization, and evaluation. Int J Pharm, 2014; 477(1–2):47–56.
33.
ParneyS, KashinathR. Effect of natural penetration enhancers on dermal delivery of hydrocortisone acetate. J Pharm Inv, 2014; 44(5):365–380.
34.
ElmowafyM, SamyA, AbdelazizAE, et al.Polymeric nanoparticles based topical gel of poorly soluble drug: Formulation, ex-vivo and in vivo evaluation. Beni-Suef Univ J Basic Appl Sci, 2017; 6(2):184–191.
35.
KalepuS, NekkantiV. Insoluble drug delivery strategies: Review of recent advances and business prospects. Acta Pharm Sin B, 2015; 5(5):442–453.
36.
RivasCJM, TarhiniM, BadriW, et al.Nanoprecipitation process: From encapsulation to drug delivery. Int J Pharm, 2017; 532(1):66–81.
37.
MiladiK, SfarS, FessiH, et al.Nanoprecipitation process: From particle preparation to in vivo applications. Polym Nanoparticles Nanomedicines A Guid their Des Prep Dev. 2016; 17–53.
38.
KhayataN, AbdelwahedW, ChehnaMF, et al.Preparation of vitamin E loaded nanocapsules by the nanoprecipitation method : From laboratory scale to large scale using a membrane contactor. Int J Pharm, 2012; 423(2):419–427.
39.
MontanheiroC, FerreiraA, MatosS, et al.Optimization of α -tocopherol loaded nanocapsules by the nanoprecipitation method. Ind Crop Prod, 2013; 50:896–903.
40.
ParkM, BalakrishnanP, YangS. Polymeric nanocapsules with SEDDS oil-core for the controlled and enhanced oral absorption of cyclosporine. Int J Pharm, 2013; 441(1–2):757–764.
41.
Moinard-ChécotD, ChevalierY, BriançonS, et al.Mechanism of nanocapsules formation by the emulsion–diffusion process. J Colloid Interface Sci, 2008; 317(2):458–468.
42.
ZylJPV, Wet-RoosDD, SandersonRD, et al.The role of surfactant in controlling particle size and stability in the miniemulsion polymerization of polymeric nanocapsules. Eur Pol J, 2004; 40:2717–2725.
43.
SeijoB, FattalE, Roblot-TreupelL, CouvreurP. Design of nanoparticles of less than 50 nm diameter : Preparation, characterization and drug loading. Int J Pharm, 1990; 62(1):1–7.
44.
ElmowafyM, ShalabyK, BadranMM, et al.Multifunctional carbamazepine loaded nanostructured lipid carrier (NLC) formulation. Int J Pharm, 2018; 550(1–2):359–371.
45.
DelgadoÁV, González-CaballeroF, HunterRJ, et al.; International Union of Pure and Applied Chemistry, Physical and Biophysical Chemistry Division IUPAC Technical Report. Measurement and interpretation of electrokinetic phenomena. J Colloid Interface Sci, 2007; 309(2):194–224.
46.
HonaryS, ZahirF. Effect of zeta potential on the properties of nano-drug delivery systems-a review (Part 2). Trop J Pharm Res, 2013; 12(2):265–273.
47.
JacobsC, KayserO, MüllerRH. Nanosuspensions as a new approach for the formulation for the poorly soluble drug tarazepide. Int J Pharm, 2000; 196(2):161–164.
AmmarHO, TadrosMI, SalamaNM, et al.Ethosome-derived invasomes as a potential transdermal delivery system for vardenafil hydrochloride: Development, optimization and application of physiologically based pharmacokinetic modeling in adults and geriatrics. Int J Nanomedicine, 2020; 15:5671–5685.
50.
PrasanthiD, K. LakshmiP. Iontophoretic transdermal delivery of finasteride in vesicular invasomal carriers. PNT, 2013; 1(2):136–150.
51.
PolettoFS, BeckRCR, GuterresSS, et al.Polymeric Nanocapsules : Concepts and Applications. In: BeckR, GuterresS, PohlmannA (eds) Nanocosmetics and Nanomedicines. 2011.
52.
GranataG, StracquadanioS, LeonardiM, et al.Essential oils encapsulated in polymer-based nanocapsules as potential candidates. Food Chem, 2018; (269):286–292.
53.
PreetzC, RübeA, ReicheI, et al.Preparation and characterization of biocompatible oil-loaded polyelectrolyte nanocapsules. Nanomedicine, 2008; 4(2):106–114.
54.
CouvreurP, BarrattG, FattalE, et al.Nanocapsule technology: A review. Crit Rev Ther Drug Carr Syst, 2002; 19(2).
55.
Mora-HuertasCE, FessiH, ElaissariA. Polymer-based nanocapsules for drug delivery. Int J Pharm, 2010; 385(1–2):113–142.
56.
CharoenputtakunP, PamornpathomkulB, OpanasopitP, et al.Terpene composited lipid nanoparticles for enhanced dermal delivery of all- trans -retinoic acids. Biol Pharm Bull, 2014; 37(7):1139–1148.
57.
BadranM, ShazlyG, El-BadryM. Effect of terpene liposomes on the transdermal delivery of hydrophobic model drug, nimesulide: Characterization, stability and in vitro skin permeation. Afr J Pharm Pharmacol, 2012; 6(43):3018–3026.
58.
KahramanE, NeşetoğluN, GüngörS, et al.The combination of nanomicelles with terpenes for enhancement of skin drug delivery. Int J Pharm, 2018; 551(1–2):133–140.
59.
JainD, AthawaleR, BajajA, et al.Studies on stabilization mechanism and stealth effect of poloxamer 188 onto PLGA nanoparticles. Colloids Surf B Biointerfaces, 2013; 109:59–67.
60.
FerreiraM, ChavesLL, LimaSAC, et al.Optimization of nanostructured lipid carriers loaded with methotrexate: A tool for inflammatory and cancer therapy. Int J Pharm, 2015; 492(1–2):65–72.
61.
Maleki DizajS, LotfipourF, Barzegar-JalaliM, et al.Application of Box–Behnken design to prepare gentamicin-loaded calcium carbonate nanoparticles. Artif Cells Nanomed Biotechnol, 2016; 44(6):1475–1481.
62.
VelagaSP, GhaderiR, CarlforsJ. Preparation and characterisation of hydrocortisone particles using a supercritical fluids extraction process. Int J Pharm, 2002; 231(2):155–166.
AmnuaikitC, IkeuchiI, OgawaraK-I, HigakiK, KimuraT. Skin permeation of propranolol from polymeric film containing terpene enhancers for transdermal use. Int J Pharm, 2005; 289(1–2):167–178.
65.
GaneshM, JeonUJ, UbaidullaU, et al.Chitosan cocrystals embedded alginate beads for enhancing the solubility and bioavailability of aceclofenac. Int J Biol Macromol, 2015; 74:310–317.
66.
FaisalW, SolimanGM, HamdanAM. Enhanced skin deposition and delivery of voriconazole using ethosomal preparations. J Liposome Res, 2018; 28(1):14–21.
67.
SalamaA, BadranM, ElmowafyM, et al.Spironolactone-loaded leciplexes as potential topical delivery systems for female acne: In vitro appraisal and ex vivo skin permeability studies. Pharmaceutics, 2020; 12(1):1–17.
68.
ChangS, BangaAK. Transdermal iontophoretic delivery of hydrocortisone from cyclodextrin solutions. J Pharm Pharmacol, 1998; 50(6):635–640.
69.
GrcicJF, VoinovichD, MoneghiniM, et al.Chitosan microspheres with hydrocortisone and hydrocortisone-hydroxypropyl-b-cyclodextrin inclusion complex. Eur J Pharm Sci, 2000; 9:373–379.
70.
MandalB, MittalNK, BalabathulaP, et al.Development and in vitro evaluation of core–shell type lipid–polymer hybrid nanoparticles for the delivery of erlotinib in non-small cell lung cancer. Eur J Pharm Sci, 2016; 81:162–171.
71.
MelloVAd, Ricci-JúniorE. Encapsulation of naproxen in nanostructured system: Structural characterization and in vitro release studies. Quím Nova, 2011; 34(6):933–939.
72.
DehkharghaniRA, HosseinzadehM, NezafatdoostF, et al.Application of methodological analysis for hydrocortisone nanocapsulation in biodegradable polyester and MTT assay. Polym Sci Ser A, 2018; 60(6):770–776.
73.
GovenderT, ChoonaraYE, KumarP, et al.A novel melt-dispersion technique for simplistic preparation of chlorpromazine-loaded polycaprolactone nanocapsules. Polymers (Basel), 2015; 7(6):1145–1176.
74.
KumarA, SawantK. Encapsulation of exemestane in polycaprolactone nanoparticles: Optimization, characterization, and release kinetics. Cancer Nanotechnol, 2013; 4(4–5):57–71.
75.
ElmowafyM, AlruwailiNK, ShalabyK, et al.Long-acting paliperidone parenteral formulations based on polycaprolactone nanoparticles; the influence of stabilizer and chitosan on in vitro release, protein adsorption, and cytotoxicity. Pharmaceutics, 2020; 12(2):160.
76.
TiwariG, SinghS, AhammedSYE, et al.Hydrocortisone-loaded lipid-polymer hybrid nanoparticles for macrophage targeted delivery in chronic obstructive pulmonary disease. IJDDT, 2024; 14(01):160–164.
77.
WangS, MaD, HuangY, et al.SYNTHESIS AND CHARACTERIZATION OF PCL/CALCINED BONE COMPOSITES. J Chil Chem Soc, 2013; 58(3):1902–1906.
78.
SawantK, PandeyA, PatelS. Aripiprazole loaded poly (caprolactone) nanoparticles : Optimization and in vivo pharmacokinetics. Mater Sci Eng C Mater Biol Appl, 2016; 66:230–243.
79.
Schmid-WendtnerM-H. Korting HC. pH and skin care. Abw Wissenschaftsverlag; 2007.
80.
BeheraB, PatilV, SagiriSS, et al.Span‐60‐based organogels as probable matrices for transdermal/topical delivery systems. J of Applied Polymer Sci, 2012; 125(2):852–863.
81.
VitorinoC, SousaJ, PaisA. Overcoming the skin permeation barrier: Challenges and opportunities. Curr Pharm Des, 2015; 21(20):2698–2712.
82.
OktayAN, KarakucukA, Ilbasmis-TamerS, et al.Dermal flurbiprofen nanosuspensions: Optimization with design of experiment approach and in vitro evaluation. Eur J Pharm Sci, 2018; 122(July):254–263.
83.
ElmowafyM. Skin penetration/permeation success determinants of nanocarriers: Pursuit of a perfect formulation. Colloids Surf B Biointerfaces, 2021; 203:111748.
SubongkotT, OpanasopitP, RojanarataT, et al.Effect of limonene and 1, 8 cineole on the skin penetration of fluorescein sodium deformable liposomes. AMR, 2012; 506:449–452.
86.
DragicevicN, MaibachHI. Percutaneous penetration enhancers chemical methods in penetration enhancement: Modification of the stratum corneum: Drug manipulation startegies and vehicle effects. 2015; 1–411.
87.
WangJ, ZhangL, ChiH, et al.An alternative choice of lidocaine-loaded liposomes : lidocaine-loaded lipid—Polymer hybrid nanoparticles for local anesthetic therapy. Drug Del, 2016:7544.
