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. 2021 Feb 19;11(2):530. doi: 10.3390/nano11020530

Table 1.

Preclinical in vivo studies where the injectable delivery approach was used for the delivery of drugs through nano-based materials in osteoporosis (OP) condition.

Reference Aim Study Design Experimental Groups Main Characteristics of Nanomaterial Main Results
Cai et al., 2017 [31] Anti-OP effect of anti-miR214 delivered by PU nanomicelles modified by the acidic peptide Asp8 injected via tail vein Female C57 BL/6 OVX mice
  • -

    Asp8-PU (200 μL);

  • -

    Asp8-PU-anti-miR214 (200 μL)

 PU nanomicelles modified by acidic peptide Asp8 (~80 nm), loaded with anti-miR214 ↑BMD, Tb.Th, Tb.N, BV/TV, SMI, ↓Tb.Sp, Oc.S/BS, Oc.N/BPm in Asp8-PU-anti-miR214 vs. Asp8-PU
Fouand-Elhady et al., 2020 [35] Anti-OP effect of nHA, nCh/HA and nAg/HA delivered intravenously Female albino Wistar OVX rats
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    nHA (8 mg/kg B.wt.);

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    nCh/HA (8 mg/kg B.wt.);

  • -

    nAg/HA (8 mg/kg B.wt.);

  • -

    alendronate (1 mg/kg B.wt.)

 nHA, nCh/HA and nAg/HA (25.5, 28.85 and 22.73 nm) ↓SOST, BALP, BSP, RANKL, CtsK and ↑calcification in all groups vs. OVX only
Kaur et al., 2019a [39] Anti-OP effect of nHA and mHA particles doped with Eu oxides injected intrafemorally Female Wistar OVX rats (DM treated)
  • -

    Eu-mHA (100 μg/kg);

  • -

    Eu-nHA (25, 50, 100 μg/kg)

 Eu-nHA and Eu-mHA (12.27 ± 0.08 and 25.29 ± 0.15) ↓ALP in all groups vs. OP only. ↑Ca, body and dry bone weight, volume, density, peak load, ultimate stiffness, Young’s modulus in all groups vs. OP only
Kettenberger et al., 2017 [41] Anti-OP effect of ZOL loaded nHA integrated in a cross-linked hyaluronic acid hydrogel (nHA-ZOL-Gel) injected in the femoral condyle Female Wistar OVX rats
  • -

    nHA-Gel;

  • -

    nHA-ZOL-Gel

 nHA-ZOL-Gel (~200 nm) ↑MV/TV, MR and ↓DR in nHA-ZOL-Gel vs. nHA-Gel
Khajuria et al., 2015 [42] Anti-OP effect of ZOL-HA nanoparticles (HNLZ)
injected intravenously		 Female Wistar OVX rats
  • -

    Saline;

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    ZOL (100 μg/kg);

  • -

    HA (100 μg/kg);

  • -

    HNLZ (25, 50, 100 μg/kg)

 HA NPs (100–130 nm) loaded with ZOL ↓BSAP, PINP, OCN, TRACP-5b, CTx, Tb.Sp, ↑BV/TV, Tb.N, Tb.Th, peak load, ultimate stiffness and strength, toughness, Young’s modulus in all groups vs. saline
Khajuria et al., 2016 [43] Anti-OP effect of RIS/ZnHA NPs injected intravenously Female Wistar OVX rats
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    saline;

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    RIS (500 μg/kg);

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    RIS/HA (250, 500 μg/kg);

  • -

    RIS/ZnHA (250, 500 μg/kg)

 ZnHA NPs (14.74 and 18.08 nm) loaded with RIS ↓BSAP, TRACP-5b, Ca, P, creatinine, Tb.Sb, ↑BV/TV, Tb.N, Tb.Th, peak load, ultimate stiffness, strength, toughness, Young’s modulus, Ca, P, Ca/P in all groups vs. saline
Khajuria et al., 2017 [44] Anti-OP effect of Sr substituted HA-ZOL (SrHA/ZOL) injected intravenously Female Wistar OVX rats
  • -

    Saline;

  • -

    ZOL (100 μg/kg);

  • -

    SrHA (100 μg/kg);

  • -

    SrHA/ZOL (25, 50, 100 μg/kg)

 SrHA NPs (31.28–40.87 nm) loaded with ZOL ↑BV/TV, Tb.N, Tb.Th, peak load, ultimate stiffness and strength, toughness, Young’s modulus and ↓BSAP, TRACP-5b, Tb.Sp in all groups vs. saline
Kotak et al., 2020 [45] Anti-OP effect of SCT loaded HA-NPs injected sublingually or subcutaneously Female Sprague Dawley OVX rats
  • -

    Saline;

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    Subcutaneous SCT injection (200 IU daily dose);

  • -

    Sublingual SCT-HA-NPs injection (200 UI daily dose)

 HA-NPs (100 nm) loaded with SCT ↓serum ALP, Ca, P, erosions, porosity, resorption pits and ↑bone density and strength in all groups vs. saline
Santhosh et al., 2019 [49] Anti-OP effect of a RIS functionalized chitosan NPs (RISCN) injected intramuscularly Female Wistar OVX rats (MP treated)
  • -

    MP;

  • -

    MP-RIS;

  • -

    MP-RISCN (250 and 350)

 RIS functionalize NPs ↑BMD, ALP in all groups vs. MP. ↑Ca in MP-RISCN vs. MP. ↑healing of trabecular microarchitecture and ↓cortical porosity on the bone surfaces of treatment groups
Sahana H et al., 2013 [50] Anti-OP effect of RIS-HA NPs (NHLR) injected intravenously Female Wistar OVX rats
  • -

    NHLR (250, 350, 500 μg/kg);

  • -

    RIS (500 μg/kg)

 NPs of HA (80–130 nm) loaded with RIS ↑BMD, maximum stress, Young’s modulus, ↓bone porosity in NHLR (250 μg/kg) vs. OVX only
Sun et al., 2016 [52] Anti-OP efficacy of Ser-Asp-Ser-Ser-Asp peptide (SDSSD)-modified PU nanomicelles to deliver anti-miR-214 to OBs injected via tail vein Female OVX mice
  • -

    SDSSD-PU-anti-scramble;

  • -

    SDSSD-PU-anti-miR-214 (siRNA dose 10 mg/kg/week)

 PU nanomicelles (70 nm) conjugated to
SDSSD peptide to encapsulate siRNA/microRNA		 ↓miR-214, ↑BMD, MAR in SDSSD-PU-anti-miR-214 vs. SDSSD-PU-anti-scramble
Wang et al., 2019 [55] Anti-OP effect of NOB-loaded PEG-PCL injected intraperitoneally C57Bl/6 OVX mice
  • -

    NOB;

  • -

    PEG-PCL;

  • -

    NOB-PEG-PCL

 PEG-PCL micelles loaded with NOB (diameter 124 nm) ↑BMD, BV/TV and ↓Tb.Sp in NOB-PEG-PCL vs. all groups
Zhang et al., 2014 [58] Anti-OP effect on alveolar bone change of N-(2-hydroxypropyl) methacrylamide NPs loaded with Asp8-(STR-R8)-Sema4d siRNA injected intravenously Female Balb/c OVX mice
  • -

    PBS;

  • -

    E2;

  • -

    Asp8-(STR-R8)-Sema4d siRNA

 Polymeric NPs loaded with Asp8-(STR-R8)-Sema4d siRNA ↑BV/TV, OBs, OCs number, ↓Sema4d, inter-molar alveolar bone height loss in Asp8-(STR-R8)-Sema4d siRNA vs. all groups

Abbreviations: OP = osteoporosis; PU = polyurethane; OVX = ovariectomy; BMD = bone-mineral density; BV/TV = bone volume/total volume; Tb.Th = trabecular thickness; Tb.Sp = trabecular spacing; Tb.N = trabecular number; SMI = structure model index; Oc.S/BS = osteoclast surface/bone surface; Oc.N/BPm = Oc number/bone perimeter; HA = hydroxyapatite; nHA = nanohydroxyapatite; nCh/HA = chitosan/hydroxyapatite nanocomposites; nAg/HA = silver/hydroxyapatite nanoparticles; SOST = serum sclerostin; BALP = bone alka-line phosphatase; BSP = bone sialoprotein; CtsK = cathepsin K; Eu = europium; mHA = microsized HA; ALP = Alkaline Phosphatase; ZOL = Zoledronate; MV/TV = Mineralized volume/tissue volume; MR = Mineralization rate; DR = Demineralization rate; BSAP = bone-specific alkaline phosphatase; PINP = procollagen type I N-terminal propeptide; TRACP-5b = tartrate-resistant acid phosphatase 5b; OCN = Osteocalcin; Ca = calcium; RIS = risedronate sodium; SCT = salmon calcitonin; Sr = strontium; MP = methylprednisolone; NOB = Nobiletin; PEG = poly(ethylene glycol); PCL = polycaprolactone; OCs = osteoclasts; OBs: osteoblasts.