In situ fabrication of alendronate-loaded calcium phosphate microspheres: Controlled release for inhibition of osteoclastogenesis

Kim, Chan Woo; Yun, Young-Pil; Lee, Hong Jae; Hwang, Yu‐Shik; Kwon, Il Keun

doi:10.1016/j.jconrel.2010.06.016

Cited by 72 publications

(58 citation statements)

References 34 publications

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“…Developed ALD-loaded CaP microspheres were found to be in size range of 163-195 mm and spherical in shape. In vitro release study showed a sustained release over 40 d, and the release showed linear kinetics with a burst release during the initial 24 h. Biological evaluation of ALD-loaded CaP microspheres showed that it directly blocked osteoclast formation by releasing ALD to monocytic precursor cells and effectively inhibited their differentiation into osteoclasts (Kim et al, 2010). This study revealed that CaP microspheres loaded with ALD showed local sustained delivery systems and CaP microspheres could serve as a good alternative to current oral formulations, increased the BA, and decreased patient discomfort due to their frequent administration and undesirable gastrointestinal effects.…”

Section: Microspheresmentioning

confidence: 97%

Bisphosphonates: therapeutics potential and recent advances in drug delivery

et al. 2014

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Context: Bisphosphonates (BPs) are widely used for prevention and treatment of osteoporosis. BPs are known as gold standard for osteoporosis (OP) treatment due to their positive results in clinical studies. But some serious side effects are associated with BPs like gastrointestinal adverse effect i.e. esophagitis and ulcer of esophagus. Oral bioavailability (BA) of BPs ranges from 0.6 to 1% due to poor absorption through gastrointestinal tract (GIT). Objective: The main objective of this review is to explore the role of novel drug delivery systems (DDSs) for the delivering of BPs and minimizing the drawbacks associated with them. Methods: The current review is focusing on classification, mechanism of action, and limitations of BPs, and is also dwelling on the use of novel DDSs like nanoparticles, liposomes, topical, transdermal systems, implants, bisphosphonate osteotropic DDS (BP-ODDS), microspheres, and calcium phosphate cements (CPCs) for BPs. This review also gives a critically reviewed compilation of the various in vitro and in vivo studies conducted till date. Conclusion: On the basis of the exhaustive literature, it has been found that the novel DDS minimizes the side effects associated with BPs and enhances the BA. The advance drug delivery has a greater impact on reducing the undesirable effects and increasing the BA of BPs.

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Section: Microspheresmentioning

confidence: 97%

Bisphosphonates: therapeutics potential and recent advances in drug delivery

et al. 2014

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“…However, most multifunctional scaffolds studied as a matrix for drug release have been shown to have rates of degradation much lower than the required rate of drug release. 40,[94][95][96] Thus, it is important to recognize that the drug release from a scaffold can be mainly controlled by the process of diffusion through it, at least during the first stages of the process. In addition, during the degradation of the scaffold, the dissolution of bioinorganic components is followed in most cases by the formation of an apatite surface layer and precipitation of HA, which will also affect the drug release kinetics.…”

Section: Bone Tissue Engineeringmentioning

confidence: 99%

“…In the case of scaffolds elaborated from bioinorganic materials, it is possible to modulate the rate of scaffold degradation by varying the chemical composition, microstructure, and percentage of crystallinity. 34,35,40,66 Further, it is important to highlight that the development of these complex systems for the delivery of BPs should involve first the characterization of the drug release kinetics in vitro. Subsequently, in vivo studies should assess the effectiveness of the 3D scaffold that acts as a matrix for in situ administration and controlled release of loaded BP, the conservation of scaffold bioactivity, the BP distribution zone, and the occurrence of possible undesirable effects, for example, if migration of the drug out of the region of interest occurs.…”

Section: Bone Tissue Engineeringmentioning

confidence: 99%

“…During the last decade, several studies that are related to the development of delivery systems for the controlled release of BP have been published. 7,29,[31][32][33][34][35][36][37][38][39][40][41] Smart methods of local drug delivery systems could increase the drug activity and specificity by concentrating the release of BP to bone sites and could reduce side effects at extra-skeletal sites. For those interested in further reading, a recent review summarizes the latest advances in the application of BPs for in situ orthopedic medication and treatments.…”

Section: Introductionmentioning

confidence: 99%

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Bisphosphonate-Based Strategies for Bone Tissue Engineering and Orthopedic Implants

Cattalini

Boccaccını

Lucangioli

et al. 2012

Tissue Engineering Part B: Reviews

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Bisphosphonates (BPs) are a group of well-established drugs that are applied in the development of metabolic bone disorder-related therapies. There is increasing interest also in the application of BPs in the context of bone tissue engineering, which is the topic of this review, in which an extensive overview of published studies on the development and applications of BPs-based strategies for bone regeneration is provided with special focus on the rationale for the use of different BPs in three-dimensional (3D) bone tissue scaffolds. The different alternatives that are investigated to address the delivery and sustained release of these therapeutic drugs in the nearby tissues are comprehensively discussed, and the most significant published approaches on bisphosphonateconjugated drugs in multifunctional 3D scaffolds as well as the role of BPs within coatings for the improved fixation of orthopedic implants are presented and critically evaluated. Finally, the authors' views regarding the remaining challenges in the fields and directions for future research efforts are highlighted.

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“…Being one of the bisphosphonates, zoledronic acid anions are suitable for coordinating calcium cations in the calcium phosphate phase through bidentate chelation. 44 The high affinity between calcium phosphate and zoledronic acid decreased the diffusion of zoledronic acid from LCP. The lipid coating added another diffusion barrier to zoledronic acid, leading to overall high encapsulation efficiency.…”

mentioning

confidence: 99%

Codelivery of zoledronic acid and double-stranded RNA from core-shell nanoparticles

Chen

Ding

Wang³

et al. 2013

IJN

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Background: Zoledronic acid, an inhibitor of osteoclast-mediated bone resorption, has been shown to have both direct and indirect antitumor activity. However, its use in extraskeletal malignancy is limited due to rapid uptake and accumulation within bone. Polyinosinic acidpolycytidylic acid [poly (I:C)] is a synthetic double-stranded RNA with direct antitumor cytotoxicity if it can be delivered to tumor cells intracellularly. Methods: Cationic lipid-coated calcium phosphate nanoparticles (LCP) were developed to enable intracellular codelivery of zoledronic acid and poly (I:C). LCP codelivering zoledronic acid and poly (I:C) were prepared using an ethanol injection method. Briefly, the ethanol solution of lipids was rapidly injected into newly formed calcium phosphate crystals containing poly (I:C) and zoledronic acid, and the mixture was then sonicated briefly to form LCP. The LCP were fully characterized for mean diameter size and zeta potential, efficiency in loading zoledronic acid, cytotoxic effect in a B16BL6 melanoma cell line in vitro, and antitumor effect in B16BL6 melanoma-bearing mice. Results: LCP with a mean diameter around 200 nm and a narrow size distribution (polydispersity index 0.17) and high zoledronic acid encapsulation efficiency (94%) were achieved. LCP loaded with zoledronic acid and poly (I:C) had significantly greater antitumor activity than the free drugs in the B16BL6 melanoma cell line (P , 0.05). Furthermore, codelivery of zoledronic acid and poly (I:C) by LCP had higher cytotoxicity than delivering poly (I:C) alone by LCP (P , 0.05), indicating a synergism between zoledronic acid and poly (I:C). Finally, the antitumor study in melanoma-bearing mice also demonstrated synergism between zoledronic acid and poly (I:C) codelivered by LCP. Conclusion: Cationic lipid-coated calcium phosphate nanoparticles constructed for codelivery of zoledronic acid and double-stranded RNA poly (I:C) had better antitumor activity both in vitro and in vivo. Future preclinical development of LCP encapsulating zoledronic acid and poly (I:C) for the treatment of human cancer is under way.

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In situ fabrication of alendronate-loaded calcium phosphate microspheres: Controlled release for inhibition of osteoclastogenesis

Cited by 72 publications

References 34 publications

Bisphosphonates: therapeutics potential and recent advances in drug delivery

Bisphosphonates: therapeutics potential and recent advances in drug delivery

Bisphosphonate-Based Strategies for Bone Tissue Engineering and Orthopedic Implants

Codelivery of zoledronic acid and double-stranded RNA from core-shell nanoparticles

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