Next Article in Journal
Correlation between Temporomandibular Disorders and Tinnitus and Possible Treatment Strategies: Comprehensive Review
Previous Article in Journal
Manipulator Smooth Control Method Based on LSTM-XGboost and Its Optimization Model Construction
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Applied Sciences
Volume 13
Issue 15
10.3390/app13158995
applsci-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Evaluation of Drug Release Profiles of Titanium Plates Coated with PLGA or Chitosan with Meropenem Using UPLC: An In Vitro Study

by
Mohammad I. Al-Qubaisey
1,*,
Rita M. Khounganian
2,
Saeed A. Syed
3 and
Sameh A. Saif
4,5
1
Department of Dentistry, Riyadh 2nd Health Cluster, Riyadh 11545, Saudi Arabia
2
Department of Oral Medicine and Diagnostic Sciences, College of Dentistry, King Saud University, Riyadh 11545, Saudi Arabia
3
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11545, Saudi Arabia
4
Department of Oral & Maxillofacial Surgery, Faculty of Dentistry, Cairo University, Cairo 12613, Egypt
5
Department of Oral & Maxillofacial Surgery, College of Dentistry, King Saud University, Riyadh 11545, Saudi Arabia
*
Author to whom correspondence should be addressed.
Appl. Sci. 2023, 13(15), 8995; https://doi.org/10.3390/app13158995
Submission received: 9 May 2023 / Revised: 6 June 2023 / Accepted: 8 June 2023 / Published: 5 August 2023
Browse Figures
Review Reports Versions Notes

Abstract

:
In some cases, titanium plates could be a reservoir for harboring bacteria resulting in challenging cases of infection. Current estimates indicate that 10–12% of plates require removal due to infection, exposure, pain, and discomfort. The present investigation was conducted to evaluate the potential sustained meropenem-coated plates amalgamated with “PLGA” polylactic co-glycolic acid and chitosan polymers with the concurrent sterilization effect of gamma irradiation. After coating the plates with either M “meropenem”, MP “meropenem-PLGA, or MC “meropenem-chitosan”, they were divided into two groups of sterile and non-sterile coated plates. The drug release was studied over three-time intervals of 1, 3, and 7 days using ultrahigh-performance liquid chromatography. Overall, the three materials had similar drug release on day one, both in sterile and non-sterile groups, while on days 3 and 7, a noticeable increase in the drug release was perceived in favor of MP. At the same time, no statistically significant difference was observed between sterile and non-sterile groups. A statistically significant increase in drug release was observed between and within the materials over time, with no overall difference between sterile and non-sterile groups.

1. Introduction

Michelet and Festal promoted mini plates for use in the repair of midface and mandibular fractures in 1972. In the late 1970s, Harle et al. popularized mini plate use in orthognathic surgery as well as in cranio-maxillofacial trauma [1]. Initially, these plates were made of highly rigid stainless steel or metal alloys. Stainless steel and other metal alloys have since fallen out of favor owing to their lack of corrosion resistance and poor biocompatibility and have been replaced by titanium [2].
Current estimates suggest that a noteworthy proportion of patients, ranging from 10 to 12%, require the removal of plates due to complications such as infection, exposure, pain, and discomfort. This is according to recent research conducted by experts in the field [3]. Moreover, the use of titanium plates and screws in surgical procedures has been shown to exhibit a failure rate of up to 10%. Furthermore, another study revealed that patients with titanium plates may experience various complaints such as plates exposure or infection, up to two decades following their operation [4]. These findings elucidate the potential difficulties and drawbacks associated with undergoing surgical procedures that utilize plates and screws.
Infections caused by microorganisms present a challenge when it comes to treatment using conventional methods, such as enteral or parenteral routes. These routes are usually effective for delivering small-molecule drugs to other infection sites [5]. However, innovative drug delivery methods are in demand as the half-life of free biomacromolecules is limited and they tend to break down and denature in physiological environments [6]. This has led to breakthroughs in biomacromolecular therapeutics, with polymeric nanoparticles made with biodegradable polymers emerging as an ideal carrier of macromolecular pharmaceuticals, owing to their advantages over conventional drug delivery vehicles [7].
Polylactic-co-glycolic-acid (PLGA) is a copolymer of lactic acid and glycolic acid that has been widely used in various biological applications, particularly in the field of medication delivery. This biodegradable and biocompatible polymer has revolutionized drug administration due to its unique properties of being able to facilitate retarded drug release over an extended period. PLGA has several advantages over other materials used for medication delivery. Firstly, it is biocompatible. This makes it an ideal candidate for medication delivery. Secondly, PLGA is biodegradable, as it will break down in the body over time into its primary components, lactic acid and glycolic acid. These metabolites are natural substances that are easily eliminated from the body, and therefore, they do not leave any toxic residues behind [8].
One of the prominent features of PLGA is its thixotropic property [9]. PLGA degradation is dependent on several factors such as its molecular weight, method of preparation; size, shape, and morphology (molecular weight, chemical structure, hydrophobicity, crystallinity, and glass transition temperature) [8,10]; physiological environment (pH, temperature and ionic strength of the environment); and site of implantation [8].
Chitosan (CH) is widely regarded as one of the most efficient natural substrates, boasting exceptional biodegradability, and is sourced from the shells of marine crustaceans. Notably, CH has become highly sought-after for its biomedical applications, primarily due to its biocompatibility, controlled biodegradability, and the nontoxic and noninflammatory properties of its byproducts. With multiple forms and structures available, CH offers a diverse range of uses. Additionally, its solubility in aqueous media makes it adept at forming films and scaffolds [11].
The characteristics of CH to be considered in the development of drug carrier systems include the degree of acetylation, molecular weight, and purity. Some of CH’s prominent features include in situ gelling, mucoadhesion, hydrophilicity, and permeability enhancement; this enables its utilization in many drug delivery systems [12].The simplicity of structural changes is one of the significant advantages of CH. This allows optimization to provide appropriate biomaterials for various therapeutic applications [13,14]. That said, CH’s effectiveness is debated as to whether it acts as a bactericidal or a bacteriostatic agent [15,16].
Meropenem (MEM) is a synthetic β-methylcarbapenem antibiotic that is categorized under the carbapenem subclass, which belongs to the β-lactam antimicrobial class. As an antimicrobial agent, it possesses an extensive spectrum of activity, with the broadest coverage among all the β-lactams [17]. The use of polymeric carriers impregnated with antimicrobial agents on titanium plates is an innovative approach to prevent infections, thereby reducing the need for additional surgeries and minimizing the risk posed to patients. It is used as an antibiotic of choice in such applications, in contrast with cephalothin, carbenicillin, amoxicillin, cefamandole, tobramycin, and vancomycin, which are more often used in coatings on bone implants [18,19,20,21,22].
As far as we know, no previous studies to date have been reported regarding PLGA and/or CH augmented with MEM as a coating for titanium plates to combat bacterial adhesion and colonization that we could use as a comparison; however, some studies were performed in the fields of dental implantology and orthopedics [23,24,25]. Thus, this study is designed to verify and investigate its efficacy. Such modified titanium plates are intended to replace their current counterparts as a prophylactic against infection in routine maxillofacial procedures and especially in reconstruction cases in which the patient may have multiple comorbidities. Ultra-high-performance liquid chromatography (UPLC) is a well-known method for separating and quantifying chemicals. It is also a simple, quick, and sensitive analytical approach that can distinguish both organic and water-soluble substances [26].
The present baseline study was carried out to quantify the drug release profiles of sterile and non-sterile coated titanium plates using UPLC to evaluate the possibility of delayed drug release within the copolymer layer over time.

2. Materials and Methods

2.1. Samples Preparation

The current investigation entailed a comprehensive examination of 54 single hole segments of low-profile MatrixMIDFACE® (Raynham, MA, USA) titanium plates, each with a thickness of 0.4 mm. The plates were manufactured by DePuy Synthes, a respected medical equipment company based in the United States.
The materials used for coating purposes were categorized into two groups:
  • Carrier: copolymers of polylactic-co-glycolic acid “PLGA” and chitosan “CH.”
  • Antibiotic: Meropenem (MEM).
The coating materials PLGA or CH and MEM were investigated using 1% w/v in acetone (Sigma-Aldrich, St. Louis, MO, USA) of each solution. They were sprayed onto the entire surface of the plates using an airbrush system (Harder & Steenbeck, Oststeinbek, Germany) [27].
In the safety cabinet, the plates were let air-dry overnight at room temperature.
The coating procedure was then carried out as follows:
Solution 1: 25 mg PLGA, and 5 mg MEM in 2.5 mL acetone.
Solution 2: 25 mg CH, and 5 mg MEM in 2.5 mL acetone.
Solution 3: 5 mg MEM in 2.5 mL acetone.
Each plate was weighed prior to and following spraying to ensure that the final modified plates contained 5 mg of MEM and 25 mg of the polymer [28].
Drug release profiles were studied on 54 MEM-coated plates, divided into two sterile and non-sterile groups each with 27 samples. They were immersed in 10 mL phosphate buffered saline (PBS) containing 5% ascorbic acid (Sigma-Aldrich, USA) as an antioxidant and incubated at 37 °C while stirring at 130 rpm (Heidolph Unimax, Schwabach Germany).
Each measurement of drug release was performed on three samples of coated plates for each time point (1, 3, and 7 days) within the three groups. Samples of the release media were extracted at the predetermined time points and replenished with fresh PBS with an antioxidant.
The MEM concentrations were measured by UPLC according to the following protocol.

2.2. Standard Preparation

All the used chemicals—acetonitrile UPLC grade, phosphoric acid 85%, chloroform—were purchased from Merck (Darmstadt, Germany).
Aqueous stock solution of MEM was prepared in 1000 µg/mL in Milli-Q water.
Calibration was performed using MEM solutions at concentrations of 1.0, 5.0, 10.0, 30.0, 50.0, 100, and 250 µg/mL. Linear regression was performed using its peak area.

2.3. UPLC Condition and Samples Processing

The analysis was performed based on sterile and non-sterile groups of 27 samples each.
The first group of the coated plates were sterilized using the standard dose of 25 kGy gamma irradiation by cobalt 60 isotope (Steris, Allershausen, Germany) [29]. Drug stability and drug release profiles for both groups were measured using chromatography on Acquity UPLC system (Waters, Milford, CT, USA), with a binary pump, vacuum degasser, a sample manager equipped with robotic auto sampler system, column oven, and photo diode array detector. Empower software (version number 2.0) was used for data acquisition and processing. The oven temperature was set to 25 °C, and the auto sampler was set to 4 °C. The stationary phase was a Waters Acquity BEH C18 UPLC column, 1.7µm, 2.1 × 100 mm with BEH C-18, 1.7 µm pre-guard column (Van Guard 2.1, 5 mm). Mobile phase “A” was 0.2% H3PO4, pH = 2.2 and mobile phase “B” was acetonitrile; 85% mobile phase “A” and 15% mobile phase “B” was used to run in an isocratic manner at a wavelength of 300 nm using a flow rate of 0.2 mL/min.
Sample results were obtained through Waters empower software using automated calculation [27,28,30].

2.4. Statistical Analysis

Quantitative data obtained from the UPLC analysis of samples from all groups at different time points were analyzed using the Statistical Package for the Social Sciences software version 26.0 (IBM Inc., Chicago, IL, USA). Descriptive statistics (mean and standard deviation) were used to express all quantitative variables. A two-way ANOVA repeated measurement was used to confirm the presence of the interaction between time and each material concentration.
A one-way ANOVA was used to compare the materials within each time point, and t-test was used to evaluate the overall difference between sterile and non-sterile groups. All assessments were carried out by one examiner and repeated three times to confirm reproducibility and reliability. The results were considered statistically significant when p ≤ 0.05.

3. Results

MEM was detected and confirmed by UPLC in all 54 samples dissolved in demineralized water with ascorbic acid. A one-way ANOVA was used to compare the materials within each time point, as shown in Table 1.
The drug release on day 1 was statistically nonsignificant in both sterile and non-sterile groups of M, MP, and MC, yielding 5.57, 6.80, and 5.82 mcg/mL in the sterile group and 5.33, 5.77, and 5.75 mcg/mL in the non-sterile group, respectively, as shown in Figure 1A–F.
An exponential statistically significant increase in drug release in both groups was noticed at day 3 and day 7 (p ≤ 0.05), as shown in Figure 2 and Figure 3.
The highest MEM concentration in all the groups was observed in sterile MC at day 7 resulting in 218.86 mcg/mL, while the lowest was in non-sterile M at day 1 by 5.33 mcg/mL, as shown in Table 1 and Figure 1D and Figure 3C.
A two-way ANOVA repeated measurement was used to confirm the presence of the interaction between time and each material concentration, as shown in Table 2, in which no statistically significant difference was noted between the materials during day 1 (p = 0.19). Statistically significant differences were perceived by days 3 and 7 (p = 0.00), as shown in Figure 2 and Figure 3.
The overall difference between the sterile and non-sterile groups was statistically nonsignificant using a t-test, except MP at day 3 and 7 (p = 0.006, 0.00), in addition to M in day 3 (p = 0.023), as shown in Table 3.

4. Discussion

The need to utilize a streamlined, quick, consistent, sensitive, and precise process of quantifying MEM trapped in a polymer layer is of utmost importance to analyze its sustained release and the sterilization effect of cobalt 60 gamma irradiation. The drug integration into the coatings and the quantity of drug release from the coatings are two key determinants that can significantly affect the efficacy of MEM. Biodegradable PLGA and CH polymers were used as coatings to fulfil those requirements [31].
Consequently, the present experiment was conducted to quantify the drug release profiles of sterile and non-sterile coated titanium plates using UPLC to evaluate the probability of delayed drug release within the copolymer layer over time. Possessing a locally present antibiotic with delayed release to prevent bacterial colonization on the titanium plate surface may be the answer to reduce and possibly eliminate the need for additional surgery to remove the source of infection.
As bacteria that form biofilm are more resistant to antimicrobial treatment than their planktonic counterparts, standard antibiotic treatments are typically ineffective at reducing infection. To date, there are no reasonable methods for eradicating the infection after it has taken place, and hardware removal is frequently the most effective solution. [32,33,34].
On day 1, it was noted that all three materials (M, MP, MC) exhibited similar levels of MEM release. However, the sterile group did show a slightly higher level of drug release compared to its non-sterile counterpart. This phenomenon can be explained by the inherent nature of polymeric carriers (PLGA and CH), which are known for their ability to act as a delayed drug release vessel as one of their prominent properties. This observation is supported by previous studies [27]. Additionally, the potential effect of cobalt 60 gamma irradiation on the sterile group cannot be ruled out as a contributing factor to the increased drug release rate. Overall, these findings suggest that the use of polymeric carriers may be a viable option for controlled drug release applications, with careful consideration given to the effects of sterilization techniques.
A statistically significant increase of MEM release from MP and MC groups occurred on day 3 and day 7 in both sterile and non-sterile samples. This is attributed to the interaction of the properties of meropenem hydrophilic nature and small molecular size [35] and the hydrophilic properties of CH. This amalgamation of CH nanospheres and MEM showed that the CH matrix would boost the drug encapsulation and retard drug release [36]. That said, PLGA has some of the characteristics of its two monomers, including the extensibility, substantially reduced hydrophobicity, and quicker disintegration of glycolic acid and the sturdiness, hydrophobicity, and slow degradation of lactic acid; thus, it showed delayed drug release on day 3 and 7 compared to day 1 [37].
A 7-day time frame was chosen to allow leeway to combat the biofilm formation ability of different bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa [38,39].
The minimal increase in the overall drug release of the cobalt 60 irradiated group can be rationalized by the possible negative irradiation effect on the performance of drug delivery systems. Irradiation dosage is one of the most important factors because irradiation may generate certain unwanted physical and chemical alterations, especially when the dosage is delivered at the conventional 25 kGy threshold. The covalent bonds may break up owing to their ionizing nature. Therefore, the applied dosage must be handled with caution [40,41,42].
No burst release effect was observed on day 1 in both the sterile and non-sterile groups, in accordance with previous studies whose authors stated this might be due to the ability of antibiotics to hinder this phenomenon as well as the effect of the neutral pH environment used in this in vitro study to simulate the clinical implementation of titanium plates directly planted in the facial bone and its surrounding tissues with neutral pH [43].
On day 3, MP in the sterile group had the highest release compared to MC and M alone, while in the non-sterile group both MP and MC had similar release that was higher than M alone. On day 7, MP in the sterile group had a higher release than MC and M, while the non-sterile group MP and MC showed similar, statistically nonsignificant release. This is attributable to the PLGA being more prone to the negative sterilization effects of gamma irradiation, while all the other variables are constant (temperature, pH, and dissolving liquid) [44].
Local administration of antibiotics at the titanium plate site could be a practical approach for combating biofilms that has several benefits, such as high local effectiveness that can be reached at the targeted location. Moreover, the local administration of antibiotics permits targeting specific microorganisms, reducing antibiotic resistance. In vitro sustained release of antibiotics has been achieved by applying various surface coatings. Certain specifications involve both antibiotics and coating materials. Regarding antibiotics, a broad antibacterial spectrum and thermostability are the most crucial characteristics [18,45].
In conclusion, the direct deposition of an antimicrobial material onto a plate’s surface prevents bacterial colonization and enables the targeted release of a therapeutic agent to prevent or treat an infection. If a biofilm develops on the plate’s surface, the therapeutic agent’s presence at the plate site can immediately increase the treatment’s efficacy. In addition, this local administration method can minimize the systemic adverse effects by decreasing the antibacterial agent dosage.
No titanium plates for craniomaxillofacial usage with antibacterial qualities are currently available on the market. Furthermore, active ingredients with limited shelf life and sensitivity to storage conditions might complicate the manufacturing process, thus delaying its time to commercialization and increasing its expense.

5. Conclusions

A statistically significant increase in meropenem release was observed between and within the M, MP, and MC over 1, 3, and 7 days, with no overall difference between the sterile and non-sterile groups.
Coating of the titanium plates with PLGA or chitosan with meropenem appeared to enhance the efficacy of the drug release as opposed to meropenem without polymers, with no significant differences between the MP and MC groups.
It is evident from the present findings that the surface treatment of titanium plates serves as a multifaceted approach to deter the occurrence of infections. However, to fully comprehend its potential benefits, it is imperative that further extensive investigations be conducted to analyze the drug release mechanism, spanning longer than seven days.

Author Contributions

Conceptualization, M.I.A.-Q. and R.M.K.; methodology, M.I.A.-Q. and S.A.S. (Saeed A. Syed); analysis, M.I.A.-Q. and S.A.S. (Saeed A. Syed); investigation, M.I.A.-Q. and S.A.S. (Saeed A. Syed); data curation, M.I.A.-Q.; writing—original draft preparation, M.I.A.-Q. and S.A.S. (Saeed A. Syed); writing—review and editing, R.M.K. and S.A.S. (Sameh A. Saif); supervision, R.M.K.; project administration, M.I.A.-Q. and R.M.K. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

This study was approved and recognized by King Saudi University, College of Dentistry Research Center (CDRC) #PR0127.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data supporting the reported results analyzed or generated during the study are available upon request from the corresponding author.

Acknowledgments

The authors wish to thank the College of Dentistry Research Center and the Deanship of Scientific Research at King Saud University, Riyadh, Saudi Arabia, for supporting and approving this research project (CDRC # PR0127). Special thanks go to the Central Laboratory staff members at King Saud University, College of Pharmacy, for their cooperation while conducting this experiment.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Haerle, F.; Champy, M.; Terry, B.C. Atlas of Craniomaxillofacial Osteosynthesis: Microplates, Miniplates, and Screws, 2nd ed.; Thieme: Stuttgart, Germany, 2009; ISBN 978-3-13-116492-6. [Google Scholar]
  2. Gupta, R.; Adeeb, N.; Griessenauer, C.J.; Moore, J.M.; Patel, A.S.; Thomas, A.J.; Ogilvy, C.S. Removal of symptomatic titanium fixation plates after craniotomy. Acta Neurochir. 2016, 158, 1845–1848. [Google Scholar] [CrossRef] [PubMed]
  3. Capucha, T.; Shilo, D.; Abdalla-Aslan, R.; Blanc, O.; Ginini, J.G.; Semel, G.; Emodi, O.; Rachmiel, A. Is open reduction internal fixation using titanium plates in the mandible as successful as we think? J. Craniofacia Surg. 2021, 33, 1032–1036. [Google Scholar] [CrossRef] [PubMed]
  4. Turvey, T.A.; Proffit, W.P.; Phillips, C. Biodegradable Fixation for Craniomaxillofacial Surgery: A 10-Year Experience Involving 761 Operations and 745 Patients. Int. J. Oral Maxillofac. Surg. 2011, 40, 244–249. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  5. Hwang, J.Y.; Li, Z.; Loh, X.J. Small Molecule Therapeutic-Loaded Liposomes as Therapeutic Carriers: From Development to Clinical Applications. RSC Adv. 2016, 6, 70592–70615. [Google Scholar] [CrossRef]
  6. Ye, C.; Chi, H. A Review of Recent Progress in Drug and Protein Encapsulation: Approaches, Applications and Challenges. Mater. Sci. Eng. C 2018, 83, 233–246. [Google Scholar] [CrossRef]
  7. Fan, X.; Jiang, S.; Li, Z.; Loh, X.J. Conjugation of Poly(Ethylene Glycol) to Poly(Lactide)-Based Polyelectrolytes: An Effective Method to Modulate Cytotoxicity in Gene Delivery. Mater. Sci. Eng. C 2017, 73, 275–284. [Google Scholar] [CrossRef]
  8. Dinarvand, R.; Sepehri, N.; Manoochehri, S.; Rouhani, H.; Atyabi, F. Polylactide-Co-Glycolide Nanoparticles for Controlled Delivery of Anticancer Agents. Int. J. Nanomed. 2011, 6, 877–895. [Google Scholar] [CrossRef] [Green Version]
  9. Lai, P.-L.; Hong, D.-W.; Lin, C.T.-Y.; Chen, L.-H.; Chen, W.-J.; Chu, I.-M. Effect of Mixing Ceramics with a Thermosensitive Biodegradable Hydrogel as Composite Graft. Compos. Part B Eng. 2012, 43, 3088–3095. [Google Scholar] [CrossRef]
  10. Rocha, C.V.; Gonçalves, V.; da Silva, M.C.; Bañobre-López, M.; Gallo, J. PLGA-based composites for various biomedical applications. Int. J. Mol. Sci. 2022, 23, 2034. [Google Scholar] [CrossRef]
  11. Ruocco, N.; Costantini, S.; Guariniello, S.; Costantini, M. Polysaccharides from the Marine Environment with Pharmacological, Cosmeceutical and Nutraceutical Potential. Molecules 2016, 21, E551. [Google Scholar] [CrossRef]
  12. Kim, S.-K. (Ed.) Chitin and Chitosan Derivatives: Advances in Drug Discovery and Developments; CRC Press Taylor & Francis: Boca Raton, FL, USA, 2014; ISBN 978-1-4665-6628-6. [Google Scholar]
  13. Abd El-Hack, M.E.; El-Saadony, M.T.; Shafi, M.E.; Zabermawi, N.M.; Arif, M.; Batiha, G.E.; Khafaga, A.F.; Abd El-Hakim, Y.M.; Al-Sagheer, A.A. Antimicrobial and antioxidant properties of chitosan and its derivatives and their applications: A Review. Int. J. Biol. Macromol. 2020, 164, 2726–2744. [Google Scholar] [CrossRef]
  14. Cesàro, A.; Bellich, B.; Borgogna, M. Biophysical Functionality in Polysaccharides: From Lego-Blocks to Nano-Particles. Eur. Biophys. J. 2012, 41, 379–395. [Google Scholar] [CrossRef]
  15. Goy, R.C.; de Britto, D.; Assis, O.B.G. A Review of the Antimicrobial Activity of Chitosan. Polímeros 2009, 19, 241–247. [Google Scholar] [CrossRef]
  16. Kong, M.; Chen, X.G.; Xing, K.; Park, H.J. Antimicrobial Properties of Chitosan and Mode of Action: A State of the Art Review. Int. J. Food Microbiol. 2010, 144, 51–63. [Google Scholar] [CrossRef]
  17. Zhanel, G.G.; Wiebe, R.; Dilay, L.; Thomson, K.; Rubinstein, E.; Hoban, D.J.; Noreddin, A.M.; Karlowsky, J.A. Comparative Review of the Carbapenems. Drugs 2007, 67, 1027–1052. [Google Scholar] [CrossRef]
  18. Darouiche, R.O. Treatment of Infections Associated with Surgical Implants. N. Engl. J. Med. 2004, 350, 1422–1429. [Google Scholar] [CrossRef] [PubMed]
  19. Salmon-Rousseau, A.; Martins, C.; Blot, M.; Buisson, M.; Mahy, S.; Chavanet, P.; Piroth, L. Comparative review of imipenem/cilastatin versus meropenem. Médecine Et Mal. Infect. 2020, 50, 316–322. [Google Scholar] [CrossRef]
  20. Novelli, A.; Del Giacomo, P.; Rossolini, G.M.; Tumbarello, M. Meropenem/vaborbactam: A next generation β-lactam β-lactamase inhibitor combination. Expert Rev. Anti-Infect. Ther. 2020, 18, 643–655. [Google Scholar] [CrossRef] [PubMed]
  21. Smith, R.J.; Bryant, R.G. Metal Substitutions Incarbonic Anhydrase: A Halide Ion Probe Study. Biochem. Biophys. Res. Commun. 1975, 66, 1281–1286. [Google Scholar] [CrossRef]
  22. Sun, C.; Wu, J.; Pan, Y. Characterization of Novel Hydrolysis Products of Carbapenems by Electrospray Ionization Mass Spectrometry: Characterization of Degradation Products of Carbapenems. Rapid Commun. Mass Spectrom. 2009, 23, 3205–3212. [Google Scholar] [CrossRef]
  23. Kaur, M.; Singh, K. Review on Titanium and Titanium Based Alloys as Biomaterials for Orthopaedic Applications. Mater. Sci. Eng. C 2019, 102, 844–862. [Google Scholar] [CrossRef] [PubMed]
  24. Alécio, A.B.W.; Ferreira, C.F.; Babu, J.; Shokuhfar, T.; Jo, S.; Magini, R.; Garcia-Godoy, F. Doxycycline Release of Dental Implants With Nanotube Surface, Coated With Poly Lactic-Co-Glycolic Acid for Extended PH-Controlled Drug Delivery. J. Oral Implantol. 2019, 45, 267–273. [Google Scholar] [CrossRef]
  25. Sun, S.; Zhang, Y.; Zeng, D.; Zhang, S.; Zhang, F.; Yu, W. PLGA Film/Titanium Nanotubues as a Sustained Growth Factor Releasing System for Dental Implants. J. Mater. Sci. Mater. Med. 2018, 29, 141. [Google Scholar] [CrossRef]
  26. Ghosh, N.; Dhepe, P.L. HPLC Method Development for Chitin and Chitosan Valorisation Chemistry. Carbohydr. Polym. Technol. Appl. 2021, 2, 100139. [Google Scholar] [CrossRef]
  27. Guillaume, O.; Garric, X.; Lavigne, J.-P.; Van Den Berghe, H.; Coudane, J. Multilayer, Degradable Coating as a Carrier for the Sustained Release of Antibiotics: Preparation and Antimicrobial Efficacy in Vitro. J. Control. Release 2012, 162, 492–501. [Google Scholar] [CrossRef]
  28. Guillaume, O.; Lavigne, J.-P.; Lefranc, O.; Nottelet, B.; Coudane, J.; Garric, X. New Antibiotic-Eluting Mesh Used for Soft Tissue Reinforcement. Acta Biomater. 2011, 7, 3390–3397. [Google Scholar] [CrossRef]
  29. Ding, D.; Zhu, Q. Recent Advances of PLGA Micro/Nanoparticles for the Delivery of Biomacromolecular Therapeutics. Mater. Sci. Eng. C Mater. Biol. Appl. 2018, 92, 1041–1060. [Google Scholar] [CrossRef]
  30. Piponski, M.; Stoimenova, T.B.; Melnyk, T.; Kovalenko, S.; Todevska, E.L.; Velkovski, M.; Deeb, S.E.; Mysula, Y.; Logoyda, L. Concepts for New Rapid Simple HPLC Method for Quantification of Fosfomycin Trometamol in Pharmaceutical Dosage Forms with Direct UV Detection. Sci. Pharm. 2022, 90, 35. [Google Scholar] [CrossRef]
  31. Rams, T.E.; Degener, J.E.; van Winkelhoff, A.J. Antibiotic Resistance in Human Peri-Implantitis Microbiota. Clin. Oral Implant. Res. 2014, 25, 82–90. [Google Scholar] [CrossRef] [Green Version]
  32. Lindsay, D.; von Holy, A. Bacterial Biofilms within the Clinical Setting: What Healthcare Professionals Should Know. J. Hosp. Infect. 2006, 64, 313–325. [Google Scholar] [CrossRef]
  33. Fux, C.A.; Costerton, J.W.; Stewart, P.S.; Stoodley, P. Survival Strategies of Infectious Biofilms. Trends Microbiol. 2005, 13, 34–40. [Google Scholar] [CrossRef] [PubMed]
  34. Stewart, P.S.; William Costerton, J. Antibiotic Resistance of Bacteria in Biofilms. Lancet 2001, 358, 135–138. [Google Scholar] [CrossRef] [PubMed]
  35. Cies, J.J.; Moore, W.S.; Enache, A.; Chopra, A. Population Pharmacokinetics and Pharmacodynamic Target Attainment of Meropenem in Critically Ill Young Children. J. Pediatr. Pharmacol. Ther. 2017, 22, 276–285. [Google Scholar] [CrossRef] [Green Version]
  36. Luo, C.; Yang, Q.; Lin, X.; Qi, C.; Li, G. Preparation and Drug Release Property of Tanshinone IIA Loaded Chitosan-Montmorillonite Microspheres. Int. J. Biol. Macromol. 2019, 125, 721–729. [Google Scholar] [CrossRef]
  37. Essa, D.; Kondiah, P.P.D.; Choonara, Y.E.; Pillay, V. The Design of Poly(Lactide-Co-Glycolide) Nanocarriers for Medical Applications. Front. Bioeng. Biotechnol. 2020, 8, 48. [Google Scholar] [CrossRef]
  38. Oliveira, M.; Nunes, S.F.; Carneiro, C.; Bexiga, R.; Bernardo, F.; Vilela, C.L. Time Course of Biofilm Formation by Staphylococcus Aureus and Staphylococcus Epidermidis Mastitis Isolates. Vet. Microbiol. 2007, 124, 187–191. [Google Scholar] [CrossRef]
  39. Al-kafaween, M.A.; Mohd Hilmi, A.B.; Jaffar, N.; Al-Jamal, H.A.N.; Zahri, M.K. Determination of Optimum Incubation Time for Formation of Pseudomonas Aeruginosa and Streptococcus Pyogenes Biofilms in Microtiter Plate. Bull. Natl. Res. Cent. 2019, 43, 100. [Google Scholar] [CrossRef] [Green Version]
  40. Sakar, F.; Özer, A.Y.; Erdogan, S.; Ekizoglu, M.; Kart, D.; Özalp, M.; Colak, S.; Zencir, Y. Nano Drug Delivery Systems and Gamma Radiation Sterilization. Pharm. Dev. Technol. 2017, 22, 775–784. [Google Scholar] [CrossRef]
  41. The Pharmacopoeial Secretariat. British Pharmacopoeia; The Pharmacopoeial Secretariat: London, UK, 2012; Volume 5. [Google Scholar]
  42. Yi, X.; Shen, M.; Liu, X.; Gu, J. Emerging strategies based on nanomaterials for ionizing radiation-optimized drug treatment of cancer. Nanoscale 2021, 13, 13943–13961. [Google Scholar] [CrossRef]
  43. Ren, Y.; Zhao, X.; Liang, X.; Ma, P.X.; Guo, B. Injectable Hydrogel Based on Quaternized Chitosan, Gelatin and Dopamine as Localized Drug Delivery System to Treat Parkinson’s Disease. Int. J. Biol. Macromol. 2017, 105, 1079–1087. [Google Scholar] [CrossRef]
  44. Shahabi, S.; Najafi, F.; Majdabadi, A.; Hooshmand, T.; Haghbin Nazarpak, M.; Karimi, B.; Fatemi, S.M. Effect of Gamma Irradiation on Structural and Biological Properties of a PLGA-PEG-Hydroxyapatite Composite. Sci. World J. 2014, 2014, 420616. [Google Scholar] [CrossRef] [PubMed]
  45. Chouirfa, H.; Bouloussa, H.; Migonney, V.; Falentin-Daudré, C. Review of Titanium Surface Modification Techniques and Coatings for Antibacterial Applications. Acta Biomater. 2019, 83, 37–54. [Google Scholar] [CrossRef]
Applsci 13 08995 g001
Figure 1. (A–F) Comparison of drug release between sterile and non-sterile M, MP, and MC groups at day 1.
Figure 1. (A–F) Comparison of drug release between sterile and non-sterile M, MP, and MC groups at day 1.
Applsci 13 08995 g001
Applsci 13 08995 g002
Figure 2. (A–F) Comparison of drug release between sterile and non-sterile M, MP, and MC groups at day 3.
Figure 2. (A–F) Comparison of drug release between sterile and non-sterile M, MP, and MC groups at day 3.
Applsci 13 08995 g002
Applsci 13 08995 g003
Figure 3. (A–F) Comparison of drug release between sterile and non-sterile M, MP, and MC groups at day 7.
Figure 3. (A–F) Comparison of drug release between sterile and non-sterile M, MP, and MC groups at day 7.
Applsci 13 08995 g003
Table 1. Comparison within each sterile and non-sterile materials (M, MP, MC) over 1, 3, and 7 days.
Table 1. Comparison within each sterile and non-sterile materials (M, MP, MC) over 1, 3, and 7 days.
MaterialTimeNMean ± SD95% Confidence Interval
Lower BoundaryUpper Boundary
Sterile
MDay 135.57 ± 0.145.215.92
Day 3355.50 ± 1.5551.6659.34
Day 73163.81± 1.06161.19166.44
MPDay 136.80 ± 1.163.929.68
Day 3373.59 ± 1.7569.2377.94
Day 73205.53 ± 1.95200.69210.38
MCDay 135.82 ± 0.564.437.21
Day 3364.81 ± 0.6063.3266.31
Day 73218.86 ± 1.67214.71223.02
Non-sterile
MDay 135.33 ± 0.184.885.77
Day 3351.10 ± 1.4647.4654.74
Day 73165.07 ± 1.77160.66169.47
MPDay 135.77 ± 0.205.286.26
Day 3362.07 ± 0.2961.3662.79
Day 73191.55 ± 0.93189.25193.84
MCDay 135.75 ± 0.434.686.83
Day 3362.17 ± 1.5258.3965.96
Day 73217.23 ± 1.92212.46222
* Statistically significant at p ≤ 0.05.
Table 2. Comparison between sterile and non-sterile materials (M, MP, MC) over time.
Table 2. Comparison between sterile and non-sterile materials (M, MP, MC) over time.
MaterialDay 1Day 3Day 7
Mean ± SDp-ValueMean ± SDp-ValueMean ± SDp-Value
Sterile
M5.57 ± 0.140.1955.50 ± 1.550.00 *163.81 ± 1.060.00 *
MP6.80 ±1.1673.59 ± 1.75205.53 ± 1.95
MC5.82 ± 0.5664.81 ± 0.60218.86 ± 1.67
Non-sterile
M5.33 ± 0.180.1951.10 ± 1.460.00 *165.07± 1.770.00 *
MP5.77 ± 0.2062.07 ± 0.29191.55 ± 0.93
MC5.77 ± 0.4362.17 ± 1.52217.23 ± 1.92
* Statistically significant at p ≤ 0.05.
Table 3. Comparison between sterile and non-sterile materials.
Table 3. Comparison between sterile and non-sterile materials.
TimeMaterialSterileNon-Sterilet-Test p-Value
Mean ± SDMean ± SD
Day 1M5.57 ± 0.145.33 ± 0.180.15
MP6.80 ± 1.165.77 ± 0.200.26
MC5.82 ± 0.565.75 ± 0.430.86
Day 3M55.50 ± 1.5551.10 ± 1.470.02 *
MP73.59 ± 1.7562.07 ± 0.290.01 *
MC64.81 ± 0.6062.17 ± 1.530.05
Day 7M163.81 ± 1.06165.07 ± 1.770.35
MP205.53 ± 1.95191.55 ± 0.930.00 *
MC218.86 ± 1.67217.23 ± 1.920.33
* Statistically significant at p ≤ 0.05.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Al-Qubaisey, M.I.; Khounganian, R.M.; Syed, S.A.; Saif, S.A. Evaluation of Drug Release Profiles of Titanium Plates Coated with PLGA or Chitosan with Meropenem Using UPLC: An In Vitro Study. Appl. Sci. 2023, 13, 8995. https://doi.org/10.3390/app13158995

AMA Style

Al-Qubaisey MI, Khounganian RM, Syed SA, Saif SA. Evaluation of Drug Release Profiles of Titanium Plates Coated with PLGA or Chitosan with Meropenem Using UPLC: An In Vitro Study. Applied Sciences. 2023; 13(15):8995. https://doi.org/10.3390/app13158995

Chicago/Turabian Style

Al-Qubaisey, Mohammad I., Rita M. Khounganian, Saeed A. Syed, and Sameh A. Saif. 2023. "Evaluation of Drug Release Profiles of Titanium Plates Coated with PLGA or Chitosan with Meropenem Using UPLC: An In Vitro Study" Applied Sciences 13, no. 15: 8995. https://doi.org/10.3390/app13158995

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop