Development, Characterization, and Evaluation of α-Mangostin-Loaded Polymeric Nanoparticle Gel for Topical Therapy in Skin Cancer

Shadab Md^{1

2

3}, Nabil A Alhakamy^{1

2

3}, Thikryat Neamatallah⁴, Samah Alshehri⁵, Md Ali Mujtaba⁶, Yassine Riadi⁷, Ammu K Radhakrishnan⁸, Habibullah Khalilullah⁹, Manish Gupta¹⁰, Md Habban Akhter¹¹

Affiliations

¹ Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
² Center of Excellence for Drug Research & Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
³ Mohamed Saeed Tamer Chair for Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁴ Department of Pharmacology & Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁵ Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁶ Department of Pharmaceutics, Faculty of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia.
⁷ Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
⁸ Jeffrey Cheah School of Medicine and Health Sciences, Monash University, Subang Jaya 47500, Malaysia.
⁹ Department of Pharmaceutical Chemistry and Pharmacognosy, Unaizah College of Pharmacy, Qassim University, Unaizah 51911, Saudi Arabia.
¹⁰ Department of Pharmaceutical Sciences, School of Health Sciences, University of Petroleum and Energy Studies (UPES), Dehradun 248007, India.
¹¹ School of Pharmaceutical and population Health Informatics (SoPPHI), DIT University, Dehradun 248009, India.

PMID: 34842729
PMCID: PMC8628708
DOI: 10.3390/gels7040230

Development, Characterization, and Evaluation of α-Mangostin-Loaded Polymeric Nanoparticle Gel for Topical Therapy in Skin Cancer

Shadab Md et al. Gels. 2021.

. 2021 Nov 24;7(4):230.

doi: 10.3390/gels7040230.

Authors

Affiliations

¹ Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
² Center of Excellence for Drug Research & Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
³ Mohamed Saeed Tamer Chair for Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁴ Department of Pharmacology & Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁵ Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁶ Department of Pharmaceutics, Faculty of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia.
⁷ Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
⁸ Jeffrey Cheah School of Medicine and Health Sciences, Monash University, Subang Jaya 47500, Malaysia.
⁹ Department of Pharmaceutical Chemistry and Pharmacognosy, Unaizah College of Pharmacy, Qassim University, Unaizah 51911, Saudi Arabia.
¹⁰ Department of Pharmaceutical Sciences, School of Health Sciences, University of Petroleum and Energy Studies (UPES), Dehradun 248007, India.
¹¹ School of Pharmaceutical and population Health Informatics (SoPPHI), DIT University, Dehradun 248009, India.

PMID: 34842729
PMCID: PMC8628708
DOI: 10.3390/gels7040230

Abstract

The aim of this study was to prepare and evaluate α-mangostin-loaded polymeric nanoparticle gel (α-MNG-PLGA) formulation to enhance α-mangostin delivery in an epidermal carcinoma. The poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were developed using the emulsion-diffusion-evaporation technique with a 3-level 3-factor Box-Behnken design. The NPs were characterized and evaluated for particle size distribution, zeta potential (mV), drug release, and skin permeation. The formulated PLGA NPs were converted into a preformed carbopol gel base and were further evaluated for texture analysis, the cytotoxic effect of PLGA NPs against B16-F10 melanoma cells, and in vitro radical scavenging activity. The nanoscale particles were spherical, consistent, and average in size (168.06 ± 17.02 nm), with an entrapment efficiency (EE) of 84.26 ± 8.23% and a zeta potential of -25.3 ± 7.1 mV. Their drug release percentages in phosphate-buffered solution (PBS) at pH 7.4 and pH 6.5 were 87.07 ± 6.95% and 89.50 ± 9.50%, respectively. The release of α-MNG from NPs in vitro demonstrated that the biphasic release system, namely, immediate release in the initial phase, was accompanied by sustained drug release. The texture study of the developed α-MNG-PLGA NPs gel revealed its characteristics, including viscosity, hardness, consistency, and cohesiveness. The drug flux from α-MNG-PLGA NPs gel and α-MNG gel was 79.32 ± 7.91 and 16.88 ± 7.18 µg/cm²/h in 24 h, respectively. The confocal study showed that α-MNG-PLGA NPs penetrated up to 230.02 µm deep into the skin layer compared to 15.21 µm by dye solution. MTT assay and radical scavenging potential indicated that α-MNG-PLGA NPs gel had a significant cytotoxic effect and antioxidant effect compared to α-MNG gel (p < 0.05). Thus, using the developed α-MNG-PLGA in treating skin cancer could be a promising approach.

Keywords: Behnken design; MTT assay; antioxidant assay; gel; polymeric nanoparticle; skin cancer; α-Mangostin.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

**Figure 1**
Chemical structure of α-MNG.

**Figure 2**
Model diagnostic plot representing linear correlation plot between predicted vs. actual, perturbation chart and interaction plot for responses particle size, Y₁ (a); entrapment efficiency, Y₂ (b) and PDI, Y₃ (c). (A = X₁ = Polymer concentration; B = X₂ = Surfactant concentration; and C = X₃ = Sonication time).

**Figure 3**
3-D response surface morphology (A–C) exemplifying comparative impact of input attributes; PLGA (% *w/v*), PVA (% *w/v*), and ST (min) on critical quality attributes; particle size (A), PDI (B) and entrapment efficiency (C).

**Figure 4**
Transmission Electron microscopy image of Particle size α-MNG-PLGA NPs.

**Figure 5**
DSC thermogram showing melting point of plain α-MNG (a); and α-MNG-PLGA NPs (b). FT-IR of plain α-MNG (c) and α-MNG-PLGA NPs (d).

**Figure 6**
Percentage α-MNG release from α-MNG-PLGA NPs, and α-MNG-dispersion in PBS, pH 7.4 (a); and 6.5 (b), respectively.

**Figure 7**
The steady state flux of α-MNG-PLGA NPs in skin permeation studies compared with flux of α-MNG gel (A). Concentration of drug retained in various layer of skin viz. stratum corneum, epidermis and dermis from α-MNG-PLGA NPs gel, α-MNG gel (Y), respectively (B). Data expressed as mean ± SD (*n = 3*) (††† p ≤ 0.01).

**Figure 8**
Confocal images of RhB solution (A,B); and RhB-PLGA NPs (C,D). Scale bar = 250 µm.

**Figure 9**
Cell viabilitystudy of α-MNG gel, α-MNG-PLGA NPs gel, blank PLGA NPs gel and blank gel at concentrations, (0, 2, 4, 8, and 12 µM) after incubation times at 24 h (A); and after 48 h (B) in skin cancer cell line. Data indicated as mean ± SD (n = 3); (* p < 0.05), (** p < 0.01) compared with α-MNG gel.

**Figure 10**
The DPPH antioxidant assay of α-MNG gel and α-MNG-PLGA gel. Antioxidant inhibition effect in percentage (A), Trolox equivalent antioxidant activity (TEAC) of α-MNG-PLGA gel compared with trolox and α-MNG gel (B). Values indicated as means ± SD (*n = 3*) analyzed by one way ANOVA with Bartlett’s test for statistical significance (*p <* 0.05).

**Figure 11**
Three-month stability assessment profile of α-MNG-PLGA NPs gel in varying temperature (5 ± 3 °C, 30 ± 2 °C, and 40 ± 2 °C) condition.

**Figure 12**
The schematic illustration of preparation of α-MNG-PLGA NPs.

See this image and copyright information in PMC

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Development, Characterization, and Evaluation of α-Mangostin-Loaded Polymeric Nanoparticle Gel for Topical Therapy in Skin Cancer

Affiliations

Development, Characterization, and Evaluation of α-Mangostin-Loaded Polymeric Nanoparticle Gel for Topical Therapy in Skin Cancer

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Grants and funding